Chronic inflammation in cancer development

Frontiers in Immunology

Volumn 2, Issue JAN, 2012, Pages

  Multhoff, Gabriele ^a,b   Molls, Michael ^a   Radons, Jürgen ^c  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b INSTITUTE OF EPIDEMIOLOGY   (Germany)

^c Multimmune GmbH   (Germany)

Author keywords

Carcinogenesis; Heat shock proteins; IL 1; Inflammation; NF B; STAT 3; Tumorigenic factors

Indexed keywords

EID: 84863601838     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2011.00098     Document Type: Review

References (253)

1. Aaltoma, S. H., Lipponen, P. K., and Kosma, V. M. (2001). Inducible nitric oxide synthase (iNOS) expression and its prognostic value in prostate cancer. Anticancer Res. 21, 3101-3106.
2. Adhami, V. M., Malik, A., Zaman, N., Sarfaraz, S., Siddiqui, I. A., Syed, D. N., Afaq, F., Pasha, F. S., Saleem, M., and Mukhtar, H. (2007). Combined inhibitory effects of green tea polyphenols and selective cyclooxygenase-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo. Clin. Cancer Res. 13, 1611-1619.
3. Aggarwal, B. B., and Gehlot, P. (2009). Inflammation and cancer: how friendly is the relationship for cancer patients? Curr. Opin. Pharmacol. 9, 351-369.
4. Akerfelt, M., Morimoto, R. I., and Sistonen, L. (2010). Heat shock factors: integrators of cell stress, development and lifespan. Nat. Rev. Mol. Cell Biol. 11, 545-555.
5. Akira, S., Uematsu, S., and Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell 124, 783-801.
6. Allen, I. C., TeKippe, E. M., Woodford, R. M., Uronis, J. M., Holl, E. K., Rogers, A. B., Herfarth, H. H., Jobin, C.,and Ting,J. P. (2010). The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J. Exp. Med. 207, 1045-1056.
7. Alshamsan, A. (2011). Induction of tolerogenic dendritic cells by IL-6-secreting CT26 colon carcinoma. Immunopharmacol. Immunotoxicol. doi: 10.3109/08923973.2011.625034. [Epub ahead of print].
8. Ambs, S., Merriam, W. G., Ogunfusika, M. O.,Bennett,W. P.,Ishibe,N.,Hussain, S. P., Tzeng, E. E., Geller, D. A., Billiar, T. R., and Harris, C. C. (1998). p53 and vascular endothelial growth factor regulate tumor growthof NOS2-expressing human carcinoma cells. Nat. Med. 4, 1371-1376.
9. Ancrile, B., Lim, K. H., and Counter, C. M. (2007). Oncogenic Rasinduced secretion of IL6 is required for tumorigenesis. Genes Dev. 21, 1714-1719.
10. Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., and Galibert, L. (1997). A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390, 175-179.
11. Angst, E., Reber, H. A., Hines, O. J., and Eibl, G. (2008). Mononuclear cell-derived interleukin-1 beta confers chemoresistance in pancreatic cancer cells by upregulation of cyclooxygenase-2. Surgery 144, 57-65.
12. Apte, R. N., Krelin, Y., Song, X., Dotan, S., Recih, E., Elkabets, M., Carmi, Y., Dvorkin, T., White, R. M., Gayvoronsky, L., Segal, S., and Voronov, E. (2006). Effects of microenvironmentand malignant cellderived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions. Eur. J. Cancer 42, 751-759.
13. Arnott, C. H., Scott, K. A., Moore, R. J., Robinson, S. C., Thompson, R. G., and Balkwill, F. R. (2004). Expression of both TNF-alpha receptor subtypes is essential for optimal skin tumour development. Oncogene 23, 1902-1910.
14. Asea, A., Kabingu, E., Stevenson, M. A., and Calderwood, S. K. (2000a). HSP70 peptidembearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5, 425-431.
15. Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C., and Calderwood, S. K. (2000b). HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6, 435-442.
16. Asea, A., Rehli, M., Kabingu, E., Boch, J. A., Bare, O., Auron, P. E., Stevenson, M. A., and Calderwood, S. K. (2002). Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028-15034.
17. Balkwill, F., and Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet 357, 539-545.
18. Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., Frohling, S., Chan, E. M., Sos, M. L., Michel, K., Mermel, C., Silver, S. J., Weir, B. A., Reiling, J. H., Sheng, Q., Gupta, P. B., Wadlow, R. C., Le, H., Hoersch, S., Wittner, B. S., Ramaswamy, S., Livingston, D. M., Sabatini, D. M., Meyerson, M., Thomas, R. K., Lander, E. S., Mesirov, J. P., Root, D. E., Gilliland, D. G., Jacks, T., and Hahn, W. C. (2009). Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108-112.
19. Basu, A., and Haldar, S. (2009). Combinatorial effect of epigallocatechin3-gallate and TRAIL on pancreatic cancer cell death. Int. J. Oncol. 34, 281-286.
20. Bauer, L., Venz, S., Junker, H., Brandt, R., and Radons, J. (2009). Nicotinamide phosphoribosyltransferase and prostaglandin H2 synthase 2 are up-regulated in human pancreatic adenocarcinoma cells after stimulation with interleukin-1. Int. J. Oncol. 35, 97-107.
21. Becker, C., Fantini, M. C., Schramm, C., Lehr, H. A., Wirtz, S., Nikolaev, A., Burg, J., Strand, S., Kiesslich, R., Huber, S., Ito, H., Nishimoto, N., Yoshizaki, K., Kishimoto, T., Galle, P. R., Blessing, M., Rose-John, S., and Neurath, M. F. (2004). TGFbeta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21, 491-501.
22. Belham, C., Wu, S., and Avruch, J. (1999). Intracellular signalling: PDK1 - a kinase at the hub of things. Curr. Biol. 9, R93-R96.
23. Ben-Neriah, Y., and Karin, M. (2011). Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat. Immunol. 12, 715-723.
24. Berger, F. G. (2004). The interleukin6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality. Breast Cancer Res. Treat. 88, 281-285.
25. Bianchi, M. E. (2007). DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81, 1-5.
26. Blanco, S., Sanz-Garcia, M., Santos, C. R., and Lazo, P. A. (2008). Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS ONE 3, e1660. doi:10.1371/journal.pone.0001660
27. Born, T. L., Thomassen, E., Bird, T. A., and Sims, J. E. (1998). Cloning of a novel receptor subunit, AcPL, required for interleukin18 signaling. J. Biol. Chem. 273, 29445-29450.
28. Botzler, C., Schmidt, J., Luz, A., Jennen, L., Issels, R., and Multhoff, G. (1998). Differential Hsp70 plasmamembrane expression on primary human tumors and metastases in mice with severe combined immunodeficiency. Int. J. Cancer 77, 942-948.
29. Brown, J. M., Corey, E., Lee, Z. D., True, L. D., Yun, T. J., Tondravi, M., and Vessella, R. L. (2001). Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57, 611-616.
30. Cahill, C. M., and Rogers, J. T. (2008). Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinasedependent AKT/IkappaB kinase alpha pathway targeting activator protein-1. J. Biol. Chem. 283, 25900-25912.
31. Calderwood, S. K. (2010). Heat shock proteins in breast cancer progression a suitable case for treatment? Int. J. Hyperthermia 26, 681-685.
32. Calderwood, S. K., and Gong, J. (2011). Molecular chaperones in mammary cancer growth and breast tumor therapy. J. Cell Biochem. doi: 10.1002/jcb.23461. [Epub ahead of print].
33. Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., and Goeddel, D.V. (1996). TRAF6 is a signal transducer for interleukin1. Nature 383, 443-446.
34. Cerella, C., Sobolewski, C., Dicato, M., and Diederich, M. (2010). Targeting COX-2 expression by natural compounds: a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy. Biochem. Pharmacol. 80, 1801-1815.
35. Chang, L., Kamata, H., Solinas, G., Luo, J. L., Maeda, S., Venuprasad, K., Liu, Y. C., and Karin, M. (2006). The E3 ubiquitin ligase itch couples JNK activation to TNFalphainduced cell death by inducing c-FLIP(L) turnover. Cell 124, 601-613.
36. Chase, M. A., Wheeler, D. S., Lierl, K. M., Hughes, V. S., Wong, H. R., and Page, K. (2007). Hsp72 induces inflammation and regulates cytokine production in airway epithelium through a TLR4and NF-kappaB-dependent mechanism. J. Immunol. 179, 6318-6324.
37. Chen, G., Sircar, K., Aprikian, A., Potti, A., Goltzman, D., and Rabbani, S. A. (2006). Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107, 289-298.
38. Chen, L., and Zhang, H. Y. (2007). Cancer preventive mechanisms of the green tea polyphenol (-)epigallocatechin-3-gallate. Molecules 12, 946-957.
39. Chen, L. F., and Greene, W. C. (2004). Shaping the nuclear action of NFkappaB. Nat. Rev. Mol. Cell Biol. 5, 392-401.
40. Chen, X., Tao, Q., Yu, H., Zhang, L., and Cao, X. (2002). Tumor cell membrane-bound heat shock protein 70 elicits antitumor immunity. Immunol. Lett. 84, 81-87.
41. Chien, Y., Kim, S., Bumeister, R., Loo, Y. M., Kwon, S. W., Johnson, C. L., Balakireva, M. G., Romeo, Y., Kopelovich, L., Gale, M. Jr., Yeaman, C., Camonis, J. H., Zhao, Y., and White, M. A. (2006). RalB GTPasemediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell 127, 157-170.
42. Chung, Y. C., and Chang, Y. F. (2003). Serum interleukin-6 levels reflect the disease status of colorectal cancer. J. Surg. Oncol. 83, 222-226.
43. Ciocca, D. R., and Calderwood, S. K. (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10, 86-103.
44. Colotta, F., Allavena, P., Sica, A., Garlanda, C., and Mantovani, A. (2009). Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30, 1073-1081.
45. Coussens, L. M., and Werb, Z. (2002). Inflammation and cancer. Nature 420, 860-867.
46. Cozen, W., Gill, P. S., Ingles, S. A., Masood, R., Martinez-Maza, O., Cockburn, M. G., Gauderman, W. J., Pike, M. C., Bernstein, L., Nathwani, B. N., Salam, M. T., Danley, K. L., Wang, W., Gage, J., Gundell Miller, S., and Mack, T. M. (2004). IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood 103, 3216-3221.
47. Cross, S. S., Harrison, R. F., Balasubramanian, S. P., Lippitt, J. M., Evans, C. A., Reed, M. W., and Holen, I. (2006). Expression of receptor activator of nuclear factor kappabeta ligand (RANKL) and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) in breast cancer, and their relations with osteoprotegerin, oestrogen receptor, and clinicopathological variables. J. Clin. Pathol. 59, 716-720.
48. De Paepe, B., Verstraeten, V. M., De Potter, C. R., and Bullock, G. R. (2002). Increased angiotensin II type-2 receptor density in hyperplasia, DCIS and invasive carcinoma of the breast is paralleled with increased iNOS expression. Histochem. Cell Biol. 117, 13-19.
49. DeNagel, D. C., and Pierce, S. K. (1992). A case for chaperones in antigen processing. Immunol. Today 13, 86-89.
50. DeNardo, D. G., Johansson, M., and Coussens, L. M. (2008). Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 27, 11-18.
51. Dinarello, C. A. (1996). Biologic basis for interleukin-1 in disease. Blood 87, 2095-2147.
52. Dinarello, C. A. (2010). Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 29, 317-329.
53. Dostert, C., Petrilli, V., Van, B. R., Steele, C., Mossman, B. T., and Tschopp, J. (2008). Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674-677.
54. Dower, S. K., and Qwarnstrom, E. E. (2003). Signalling networks, inflammation and innate immunity. Biochem. Soc. Trans. 31, 1462-1471.
55. Downward, J. (2009). Cancer: a tumour gene's fatal flaws. Nature 462, 44-45.
56. Dunne, A., and O'Neill, L. A. (2003). The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE 2003, re3.
57. Elgert, K. D., Alleva, D. G., and Mullins, D. W. (1998). Tumorinduced immune dysfunction: the macrophage connection. J. Leukoc. Biol. 64, 275-290.
58. El-Osta, H., Janku, F., and Kurzrock, R. (2010). Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (Anakinra). Mol. Cancer Ther. 9, 1485-1488.
59. Fahy, B. N., Schlieman, M. G., Virudachalam, S., and Bold, R. J. (2004). Inhibition of AKT abrogates chemotherapy-induced NF-kappaB survival mechanisms: implications for therapy in pancreatic cancer. J. Am. Coll. Surg. 198, 591-599.
60. Fernandez, M., Pino, A. M., Figueroa, P., and Rodriguez, J. P. (2010). The increased expression of receptor activator of nuclear-kappaB ligand (RANKL) of multiple myeloma bone marrow stromal cells is inhibited by the bisphosphonate ibandronate. J. Cell. Biochem. 111, 130-137.
61. Fernandez-Medarde, A., and Santos, E. (2011). Ras in cancer and developmental diseases. Genes Cancer 2, 344-358.
62. Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., Teague, J. W., Campbell, P. J., Stratton, M. R., and Futreal, P. A. (2011). COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39, D945-D950.
63. Franchi, L., Eigenbrod, T., Munoz Planillo, R., and Nunez, G. (2009). The inflammasome: a caspase-1activation platform that regulates immune responses and disease pathogenesis. Nat. Immunol. 10, 241-247.
64. Garcea, G., Dennison, A. R., Steward, W. P., and Berry, D. P. (2005). Role of inflammation in pancreatic carcinogenesis and the implications for future therapy. Pancreatology 5, 514-529.
65. Gastpar, R., Gehrmann, M., Bausero, M. A., Asea, A., Gross, C., Schroeder, J. A., and Multhoff, G. (2005). Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 65, 5238-5247.
66. Gastpar, R., Gross, C., Rossbacher, L., Ellwart, J., Riegger, J., and Multhoff, G. (2004). The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells. J. Immunol. 172, 972-980.
67. Gay, N. J., Gangloff, M., and O'Neill, L. A. (2011). What the Myddosome structure tells us about the initiation of innate immunity. Trends Immunol. 32, 104-109.
68. Gehrmann, M., Liebisch, G., Schmitz, G., Anderson, R., Steinem, C., De Maio, A., Pockley, G., and Multhoff, G. (2008). Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. PLoS ONE 3, e1925. doi:10.1371/journal.pone.0001925
69. Gehrmann, M., Schmetzer, H., Eissner, G., Haferlach, T., Hiddemann, W., and Multhoff, G. (2003). Membrane-bound heat shock protein 70 (Hsp70) in acute myeloid leukemia: a tumor specific recognition structure for the cytolytic activity of autologous NK cells. Haematologica 88, 474-476.
70. Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., Vermaelen, K., Panaretakis, T., Mignot, G., Ullrich, E., Perfettini, J. L., Schlemmer, F., Tasdemir, E., Uhl, M., Genin, P., Civas, A., Ryffel, B., Kanellopoulos, J., Tschopp, J., Andre, F., Lidereau, R., McLaughlin, N. M., Haynes, N. M., Smyth, M. J., Kroemer, G., and Zitvogel, L. (2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL1beta-dependent adaptive immunity against tumors. Nat. Med. 15, 1170-1178.
71. Goldbach-Mansky, R., Dailey, N. J., Canna, S. W., Gelabert, A., Jones, J., Rubin, B. I., Kim, H. J., Brewer, C., Zalewski, C., Wiggs, E., Hill, S., Turner, M. L., Karp, B. I., Aksentijevich, I., Pucino, F., Penzak, S. R., Haverkamp, M. H., Stein, L., Adams, B. S., Moore, T. L., Fuhlbrigge, R. C., Shaham, B., Jarvis, J. N., O'Neil, K., Vehe, R. K., Beitz, L. O., Gardner, G., Hannan, W. P., Warren, R. W., Horn, W., Cole, J. L., Paul, S. M., Hawkins, P. N., Pham, T. H., Snyder, C., Wesley, R. A., Hoffmann, S. C., Holland, S. M., Butman, J. A., and Kastner, D. L. (2006). Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N. Engl. J. Med. 355, 581-592.
72. Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z. W., Egan, L. J., Kagnoff, M. F., and Karin, M. (2004). IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285-296.
73. Grivennikov, S. I., and Karin, M. (2010). Inflammation and oncogenesis: a vicious connection. Curr. Opin. Genet. Dev. 20, 65-71.
74. Grosch, S., Maier, T. J., Schiffmann, S., and Geisslinger, G. (2006). Cyclooxygenase-2 (COX-2)independent anticarcinogenic effects of selective COX-2 inhibitors. J. Natl. Cancer Inst. 98, 736-747.
75. Gross, C., Hansch, D., Gastpar, R., and Multhoff, G. (2003a). Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol. Chem. 384, 267-279.
76. Gross, C., Koelch, W., DeMaio, A., Arispe, N., and Multhoff, G. (2003b). Cell surface-bound heat shock protein 70 (Hsp70) mediates perforinindependent apoptosis by specific binding and uptake of granzyme B. J. Biol. Chem. 278, 41173-41181.
77. Gross, C., Schmidt-Wolf, I. G., Nagaraj, S., Gastpar, R., Ellwart, J., Kunz Schughart, L. A., and Multhoff, G. (2003c). Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells. Cell Stress Chaperones 8, 348-360.
78. Hacker, H., and Karin, M. (2006). Regulation and function of IKK and IKK-related kinases. Sci. STKE 2006, re13.
79. Hanahan, D., and Weinberg, R. A. (2000). The hallmarks of cancer. Cell 100, 57-70.
80. Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674.
81. Härdtner, C., Brandt, R., Multhoff, G., and Radons, J. (2009). (-)Epigallocatechin-3-gallate compensates for celecoxib-mediated upregulation of PGHS-2 expression in human pancreatic adenocarcinoma cells under tumor-associated inflammatory conditions. Eur. J. Immunol. 39(Suppl. 1/09), 530-531.
82. Hartl, F. U. (1996). Molecular chaperones in cellular protein folding. Nature 381, 571-579.
83. Hedrich, C. M., Bruck, N., Fiebig, B., and Gahr, M. (2011). Anakinra: a safe and effective first-line treatment in systemic onset juvenile idiopathic arthritis (SoJIA). Rheumatol. Int. doi: 10.1007/s00296-011-22494. [Epub ahead of print].
84. Hefler, L. A., Grimm, C., Lantzsch, T., Lampe, D., Leodolter, S., Koelbl, H., Heinze, G., Reinthaller, A., Tong-Cacsire, D., Tempfer, C., and Zeillinger, R. (2005). Interleukin1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women. Clin. Cancer Res. 11, 5718-5721.
85. Herfs, M., Herman, L., Hubert, P., Minner, F., Arafa, M., Roncarati, P., Henrotin, Y., Boniver, J., and Delvenne, P. (2009). High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigenpresenting cells. Cancer Immunol. Immunother. 58, 603-614.
86. Hofbauer, L. C., and Schoppet, M. (2004). Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292, 490-495.
87. Hoffman, H. M., Throne, M. L., Amar, N. J., Sebai, M., Kivitz, A. J., Kavanaugh, A., Weinstein, S. P., Belomestnov, P., Yancopoulos, G. D., Stahl, N., and Mellis, S. J. (2008). Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 58, 2443-2452.
88. Hoffmann, J., Junker, H., Schmieder, A., Venz, S., Brandt, R., Multhoff, G., Falk, W., and Radons, J. (2011). EGCG downregulates IL1RI expression and suppresses IL-1-induced tumorigenic factors in human pancreatic adenocarcinoma cells. Biochem. Pharmacol. 82, 1153-1162.
89. Hudson, B. I., Carter, A. M., Harja, E., Kalea, A. Z., Arriero, M., Yang, H., Grant, P. J., and Schmidt, A. M. (2008). Identification, classification, and expression of RAGE gene splice variants. FASEB J. 22, 1572-1580.
90. Hussain, S. P., and Harris, C. C. (2007). Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer 121, 2373-2380.
91. Hwang, W., Jung, K., Jeon, Y., Yun, S., Kim, T. W., and Choi, I. (2010). Knockdown of the interleukin-6 receptor alpha chain of dendritic cell vaccines enhances the therapeutic potential against IL-6 producing tumors. Vaccine 29, 34-44.
92. Hwang, Y. S., Lee, S. K., Park, K. K., and Chung, W. Y. (2011). Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral Oncol. doi:10.1016/j.oraloncology.2011.08. 022. [Epub ahead of print].
93. Hynes,N. E.,and Stern,D. F. (1994). The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim. Biophys. Acta 1198, 165-184.
94. Inaba, H., Nagaoka, Y., Kushima, Y., Kumagai, A., Matsumoto, Y., Sakaguchi, M., Baba, K., and Uesato, S. (2008). Comparative examination of anti-proliferative activities of (-)-epigallocatechin gallate and (-)-epigallocatechin against HCT116 colorectal carcinoma cells. Biol. Pharm. Bull. 31, 79-84.
95. Ito, H., Takazoe, M., Fukuda, Y., Hibi, T., Kusugami, K., Andoh, A., Matsumoto, T., Yamamura, T., Azuma, J., Nishimoto, N., Yoshizaki, K., Shimoyama, T., and Kishimoto, T. (2004). A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 126, 989-996.
96. Jaiswal, M., LaRusso, N. F., and Gores, G. J. (2001). Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G626-G634.
97. Jefferies, C. A., and O'Neill, L. A. (2000). Rac1 regulates interleukin 1-induced nuclear factor kappaB activation in an inhibitory protein kappaBalpha-independent manner by enhancing the ability of the p65 subunit to transactivate gene expression. J. Biol. Chem. 275, 3114-3120.
98. Jendrossek, V. (2011). Targeting apoptosis pathways by celecoxib in cancer. Cancer Lett. doi: 10.1016/j.canlet.2011.01.012. [Epub ahead of print].
99. Jimeno, A., Amador, M. L., Kulesza, P., Wang, X., Rubio-Viqueira, B., Zhang, X., Chan, A., Wheelhouse, J., Kuramochi, H., Tanaka, K., Danenberg, K., Messersmith, W. A., Almuete, V., Hruban, R. H., Maitra, A.,Yeo, C. J., and Hidalgo, M. (2006). Assessment of celecoxib pharmacodynamics in pancreatic cancer. Mol. Cancer Ther. 5, 3240-3247.
100. Johnson, A. J., Hsu, A. L., Lin, H. P., Song, X.,and Chen,C. S. (2002). The cyclo-oxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulum Ca2+-ATPases: a plausible link with its anti-tumour effect and cardiovascular risks. Biochem. J. 366, 831-837.
101. Jura, N., Archer, H., and Bar-Sagi, D. (2005). Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between. Cell Res. 15, 72-77.
102. Jurado, S., Garcia-Giralt, N., Diez-Perez, A., Esbrit, P., Yoskovitz, G., Agueda, L., Urreizti, R., Perez-Edo, L., Salo, G., Mellibovsky, L., Balcells, S., Grinberg, D., and Nogues, X. (2010). Effect of IL-1beta,PGE(2),and TGFbeta1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts. J. Cell. Biochem. 110, 304-310.
103. Kai, H., Kitadai, Y., Kodama, M., Cho, S., Kuroda, T., Ito, M., Tanaka, S., Ohmoto, Y., and Chayama, K. (2005). Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res. 25, 709-713.
104. Kamal, A., Thao, L., Sensintaffar, J., Zhang, L., Boehm, M. F., Fritz, L. C., and Burrows, F. J. (2003). A highaffinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425, 407-410.
105. Kamata, H., Honda, S., Maeda, S., Chang, L., Hirata, H., and Karin, M. (2005). Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120, 649-661.
106. Karin, M. (2006). Nuclear factorkappaB in cancer development and progression. Nature 441, 431-436.
107. Karin, M., Cao, Y., Greten, F. R., and Li, Z. W. (2002). NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer 2, 301-310.
108. Karin, M., Lawrence, T., and Nizet, V. (2006). Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell 124, 823-835.
109. Kawai, T., and Akira, S. (2011). Tolllike receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34, 637-650.
110. Kawata, M., Koinuma, D., Ogami, T., Umezawa, K., Iwata, C., Watabe, T., and Miyazono, K. (2011). TGF-betainduced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by proinflammatory cytokines derived from RAW 264.7 macrophage cells. J. Biochem. doi: 10.1093/jb/mvr136. [Epub ahead of print].
111. Keating, S. E., Maloney, G. M., Moran, E. M., and Bowie, A. G. (2007). IRAK-2 participates in multiple tolllike receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination. J. Biol. Chem. 282, 33435-33443.
112. Khaleque, M. A., Bharti, A., Sawyer, D., Gong, J., Benjamin, I. J., Stevenson, M. A., and Calderwood, S. K. (2005). Induction of heat shock proteins by heregulin beta1 leads to protection from apoptosis and anchorageindependent growth. Oncogene 24, 6564-6573.
113. Kim, L. S., and Kim, J. H. (2011). Heat shock protein as molecular targets for breast cancer therapeutics. J. Breast Cancer 14, 167-174.
114. Kishimoto, K., Matsumoto, K., and Ninomiya-Tsuji, J. (2000). TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J. Biol. Chem. 275, 7359-7364.
115. Klein, B., Lu, Z. Y., Gaillard, J. P., Harousseau, J. L., and Bataille, R. (1992). Inhibiting IL-6 in human multiple myeloma. Curr. Top. Microbiol. Immunol. 182, 237-244.
116. Kobayashi, S.,Werneburg, N. W., Bronk, S. F., Kaufmann, S. H., and Gores, G. J. (2005). Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Aktsignaling pathway in cholangiocarcinoma cells. Gastroenterology 128, 2054-2065.
117. Kong, G., Kim, E. K., Kim, W. S., Lee, K. T., Lee, Y. W., Lee, J. K., Paik, S. W., and Rhee, J. C. (2002). Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer. J. Gastroenterol. Hepatol. 17, 914-921.
118. Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., Niu, G., Kay, H., Mule, J., Kerr, W. G., Jove, R., Pardoll, D., and Yu, H. (2005). Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 11, 1314-1321.
119. Kulp, S. K., Yang, Y. T., Hung, C. C., Chen, K. F., Lai, J. P., Tseng, P. H., Fowble, J. W., Ward, P. J., and Chen, C. S. (2004). 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2independent target for celecoxib in prostate cancer cells. Cancer Res. 64, 1444-1451.
120. Kumar, A., Xu, J., Brady, S., Gao, H., Yu, D., Reuben, J., and Mehta, K. (2010). Tissue transglutaminase promotes drug resistance and invasion by inducing mesenchymal transition in mammary epithelial cells. PLoS ONE 5, e13390. doi:10.1371/journal.pone.0013390
121. Kundu, J. K., and Surh, Y. J. (2008). Inflammation: gearing the journey to cancer. Mutat. Res. 659, 15-30.
122. Lachmann, H. J., Kone-Paut, I., Kuemmerle-Deschner, J. B., Leslie, K. S., Hachulla, E., Quartier, P., Gitton, X., Widmer, A., Patel, N., and Hawkins, P. N. (2009a). Use of canakinumab in the cryopyrinassociated periodic syndrome. N. Engl.J.Med.360, 2416-2425.
123. Lachmann, H. J., Lowe, P., Felix, S. D., Rordorf, C., Leslie, K., Madhoo, S., Wittkowski, H., Bek, S., Hartmann, N., Bosset, S., Hawkins, P. N., and Jung, T. (2009b). In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J. Exp. Med. 206, 1029-1036.
124. Ladetto, M., Vallet, S., Trojan, A., Dell'Aquila, M., Monitillo, L., Rosato, R., Santo, L., Drandi, D., Bertola, A., Falco, P., Cavallo, F., Ricca, I., De, M. F., Mantoan, B., Bode-Lesniewska, B., Pagliano, G., Francese, R., Rocci, A., Astolfi, M., Compagno, M., Mariani, S., Godio, L., Marino, L., Ruggeri, M., Omede, P., Palumbo, A., and Boccadoro, M. (2005). Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome. Blood 105, 4784-4791.
125. Lambert, J. D., Hong, J.,Yang, G.Y., Liao, J., and Yang, C. S. (2005). Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr. 81, 284S- 291S.
126. Lee, H., Herrmann, A., Deng, J. H., Kujawski, M., Niu, G., Li, Z., Forman, S., Jove, R., Pardoll, D. M., and Yu, H. (2009). Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell 15, 283-293.
127. Lee, Y. H., Ji, J. D., and Song, G. G. (2007). Adjusted indirect comparison of celecoxib versus rofecoxib on cardiovascular risk. Rheumatol. Int. 27, 477-482.
128. Lewis, A. M., Varghese, S., Xu, H., and Alexander,H. R. (2006). Interleukin1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J. Transl. Med. 4, 48.
129. Li, J., Sarosi, I., Yan, X. Q., Morony, S., Capparelli, C., Tan, H. L., McCabe, S., Elliott, R., Scully, S., Van, G., Kaufman, S., Juan, S. C., Sun, Y., Tarpley, J., Martin, L., Christensen, K., McCabe, J., Kostenuik, P., Hsu, H., Fletcher, F., Dunstan, C. R., Lacey, D. L., and Boyle, W. J. (2000). RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc. Natl. Acad. Sci. U.S.A. 97, 1566-1571.
130. Li, X., Kim, K. W., Cho, M. L., Ju, J. H., Kang, C. M., Oh, H. J., Min, J. K., Lee, S. H., Park, S. H., and Kim, H. Y. (2010). IL-23 induces receptor activator of NF-kappaB ligand expression in fibroblast-like synoviocytes via STAT3 and NF-kappaB signal pathways. Immunol. Lett. 127, 100-107.
131. Lin, W. J., and Yeh, W. C. (2005). Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24, 206-209.
132. Lin, W. W., and Karin, M. (2007). A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 117, 1175-1183.
133. Lindquist, S., and Craig, E. A. (1988). The heat-shock proteins. Annu. Rev. Genet. 22, 631-677.
134. Lu, H., Ouyang, W., and Huang, C. (2006). Inflammation, a key event in cancer development. Mol. Cancer Res. 4, 221-233.
135. Lust, J. A., Lacy, M. Q., Zeldenrust, S. R., Dispenzieri, A., Gertz, M. A., Witzig, T. E., Kumar, S., Hayman, S. R., Russell, S. J., Buadi, F. K., Geyer, S. M., Campbell, M. E., Kyle, R. A., Rajkumar, S. V., Greipp, P. R., Kline, M. P., Xiong, Y., Moon-Tasson, L. L., and Donovan, K. A. (2009). Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin. Proc. 84, 114-122.
136. Maier, T. J., Schilling, K., Schmidt, R., Geisslinger, G., and Grosch, S. (2004). Cyclooxygenase-2 (COX-2)dependent and -independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Biochem. Pharmacol. 67, 1469-1478.
137. Mantovani, A., Allavena, P., Sica, A., and Balkwill, F. (2008). Cancer-related inflammation. Nature 454, 436-444.
138. Martin, M. U., and Wesche, H. (2002). Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim. Biophys. Acta 1592, 265-280.
139. Martinon, F., Burns, K., and Tschopp, J. (2002). The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10, 417-426.
140. Matzinger, P. (1998). An innate sense of danger. Semin. Immunol. 10, 399-415.
141. Menu, P., and Vince, J. E. (2011). The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. Clin. Exp. Immunol. 166, 1-15.
142. Merati, K., Said, S. M., Andea, A., Sarkar, F., Ben-Josef, E., Mohammad, R., Philip, P., Shields, A. F., Vaitkevicius, V., Grignon, D. J., and Adsay, N. V. (2001). Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters. Am. J. Clin. Oncol. 24, 447-452.
143. Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., and Jacks, T. (2009). Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 462, 104-107.
144. Mizel, S. B. (1982). Interleukin 1 and T cell activation. Immunol. Rev. 63, 51-72.
145. Mocellin, S., Rossi, C. R., Pilati, P., and Nitti, D. (2005). Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev. 16, 35-53.
146. Molina, M. A., Sitja-Arnau, M., Lemoine, M. G., Frazier, M. L., and Sinicrope, F. A. (1999). Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 59, 4356-4362.
147. Mori, K., Berreur, M., Blanchard, F., Chevalier, C., Guisle-Marsollier, I., Masson, M., Redini, F., and Heymann, D. (2007a). Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol. Rep. 18, 1365-1371.
148. Mori, K., Le Goff, B., Berreur, M., Riet, A., Moreau,A., Blanchard, F., Chevalier, C., Guisle-Marsollier, I., Leger, J., Guicheux, J., Masson, M., Gouin, F., Redini, F., and Heymann, D. (2007b). Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B. J. Pathol. 211, 555-562.
149. Mori, T., Miyamoto, T., Yoshida, H., Asakawa, M., Kawasumi, M., Kobayashi, T., Morioka, H., Chiba, K., Toyama, Y., and Yoshimura, A. (2011). IL-1β and TNFα-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. Int. Immunol. 23, 701-712.
150. Moser, C., Schmidbauer, C., Gurtler, U., Gross, C., Gehrmann, M., Thonigs, G., Pfister, K., and Multhoff, G. (2002). Inhibition of tumor growth in mice with severe combined immunodeficiency is mediated by heat shock protein 70 (Hsp70)peptide-activated, CD94 positive natural killer cells. Cell Stress Chaperones 7, 365-373.
151. Multhoff, G., Botzler, C., Jennen, L., Schmidt, J., Ellwart, J., and Issels, R. (1997). Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J. Immunol. 158, 4341-4350.
152. Multhoff, G., Botzler, C., Wiesnet, M., Eissner, G., and Issels, R. (1995a). CD3large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells. Blood 86, 1374-1382.
153. Multhoff, G., Botzler, C., Wiesnet, M., Muller, E., Meier, T., Wilmanns, W., and Issels, R. D. (1995b). A stressinducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int. J. Cancer 61, 272-279.
154. Multhoff, G., Mizzen, L., Winchester, C. C., Milner, C. M., Wenk, S., Eissner, G., Kampinga, H. H., Laumbacher, B., and Johnson, J. (1999). Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. Exp. Hematol. 27, 1627-1636.
155. Multhoff, G., Pfister, K., Botzler, C., Jordan, A., Scholz, R., Schmetzer, H., Burgstahler, R., and Hiddemann, W. (2000). Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors. Int. J. Cancer 88, 791-797.
156. Multhoff, G., Pfister, K., Gehrmann, M., Hantschel, M., Gross, C., Hafner, M., and Hiddemann, W. (2001). A 14mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress Chaperones 6, 337-344.
157. Murshid, A., Gong, J., Stevenson, M. A., and Calderwood, S. K. (2011). Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come. Expert Rev. Vaccines 10, 1553-1568.
158. Muthuswamy, R., Mueller-Berghaus, J., Haberkorn, U., Reinhart, T. A., Schadendorf, D., and Kalinski, P. (2010). PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. Blood 116, 1454-1459.
159. Muzio, M., Ni, J., Feng, P., and Dixit, V. M. (1997). IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278, 1612-1615.
160. Nakata, Y., Matsuda, K., Uzawa, A., Nomura, M., Akashi, M., and Suzuki, G. (1995). Administration of recombinant human IL-1 by Staphylococcus enterotoxin B prevents tolerance induction in vivo. J. Immunol. 155, 4231-4235.
161. Neckers, L., and Lee, Y. S. (2003). Cancer: the rules of attraction. Nature 425, 357-359.
162. Ng, P. K., Tsui, S. K., Lau, C. P., Wong, C. H., Wong, W. H., Huang, L., and Kumta, S. M. (2010). CCAAT/enhancer binding protein beta is up-regulated in giant cell tumor of bone and regulates RANKL expression. J. Cell. Biochem. 110, 438-446.
163. Niederberger, E., Tegeder, I., Vetter, G., Schmidtko,A., Schmidt, H., Euchenhofer, C., Brautigam, L., Grosch, S., and Geisslinger, G. (2001). Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-kappaB. FASEB J. 15, 1622-1624.
164. Ninomiya-Tsuji, J., Kishimoto, K., Hiyama, A., Inoue, J., Cao, Z., and Matsumoto, K. (1999). The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398, 252-256.
165. Nishimoto, N., Kanakura,Y., Aozasa, K., Johkoh, T., Nakamura, M., Nakano, S., Nakano, N., Ikeda, Y., Sasaki, T., Nishioka, K., Hara, M., Taguchi, H., Kimura, Y., Kato, Y., Asaoku, H., Kumagai, S., Kodama, F., Nakahara, H., Hagihara, K., Yoshizaki, K., and Kishimoto, T. (2005). Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 106, 2627-2632.
166. Nishimoto, N., Yoshizaki, K., Miyasaka, N., Yamamoto, K., Kawai, S., Takeuchi, T., Hashimoto, J., Azuma, J., and Kishimoto, T. (2004). Treatment of rheumatoid arthritis with humanized antiinterleukin-6 receptor antibody: a multicenter, double-blind, placebocontrolled trial. Arthritis Rheum. 50, 1761-1769.
167. Offner, F. A., Obrist, P., Stadlmann, S., Feichtinger, H., Klingler, P., Herold, M., Zwierzina, H., Hittmair, A., Mikuz, G., and Abendstein, B. (1995). IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells. Cytokine 7, 542-547.
168. Okamoto, M., Liu, W., Luo, Y., Tanaka, A., Cai, X., Norris, D. A., Dinarello, C. A., and Fujita, M. (2010). Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase1 processing and secretion of interleukin-1beta. J. Biol. Chem. 285, 6477-6488.
169. O'Neill, L. A. (2000). The interleukin1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE 2000, re1.
170. O'Sullivan, B. J., Thomas, H. E., Pai, S., Santamaria, P., Iwakura, Y., Steptoe, R. J., Kay, T. W., and Thomas, R. (2006). IL-1 beta breaks tolerance through expansion of CD25+ effector T cells. J. Immunol. 176, 7278-7287.
171. Paduch, R., Jakubowicz-Gil, J., and Kandefer-Szerszen, M. (2009). Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGFbeta1 and/or CPT-11. J. Biosci. 34, 927-940.
172. Park, H. R., Min, S. K., Cho, H. D., Kim, D. H., Shin, H. S., and Park, Y. E. (2003). Expression of osteoprotegerin and RANK ligand in breast cancer bone metastasis. J. Korean Med. Sci. 18, 541-546.
173. Peters,M.,Muller,A. M.,and Rose-John, S. (1998). Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92, 3495-3504.
174. Pfister, K., Radons, J., Busch, R., Tidball, J. G., Pfeifer, M., Freitag, L., Feldmann, H. J., Milani, V., Issels, R., and Multhoff, G. (2007). Patient survival by Hsp70 membrane phenotype: association with different routes of metastasis. Cancer 110, 926-935.
175. Pidgeon, G. P., Harmey, J. H., Kay, E., Da Costa, M., Redmond, H. P., and Bouchier-Hayes, D. J. (1999). The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease. Br. J. Cancer 81, 1311-1317.
176. Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E., and Ben-Neriah, Y. (2004). NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461-466.
177. Pirkkala, L., Nykanen, P., and Sistonen, L. (2001). Roles of the heat shock transcription factors in regulation of the heat shock response and beyond. FASEB J. 15, 1118-1131.
178. Rabe, B., Chalaris, A., May, U., Waetzig, G. H., Seegert, D., Williams, A. S., Jones, S. A., Rose-John, S., and Scheller, J. (2008). Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 111, 1021-1028.
179. Radons, J., Dove, S., Neumann, D., Altmann, R., Botzki, A., Martin, M. U., and Falk, W. (2003). The interleukin 1 (IL-1) receptor accessory protein Toll/IL-1 receptor domain: analysis of putative interaction sites in vitro mutagenesis and molecular modeling. J. Biol. Chem. 278, 49145-49153.
180. Radons, J., Gabler, S., Wesche, H., Korherr, C., Hofmeister, R., and Falk, W. (2002). Identification of essential regions in the cytoplasmic tail of interleukin-1 receptor accessory protein critical for interleukin1 signaling. J. Biol. Chem. 277, 16456-16463.
181. Raut, C. P., Nawrocki, S., Lashinger, L. M., Davis, D. W., Khanbolooki, S., Xiong, H., Ellis, L. M., and McConkey, D. J. (2004). Celecoxib inhibits angiogenesis by inducing endothelial cell apoptosis in human pancreatic tumor xenografts. Cancer Biol. Ther. 3, 1217-1224.
182. Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., and Bedi, A. (2000). Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 14, 34-44.
183. Reddy, S. A., Huang, J. H., and Liao, W. S. (1997). Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 activation. J. Biol. Chem. 272, 29167-29173.
184. Rose-John, S., Scheller, J., Elson, G., and Jones, S. A. (2006). Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J. Leukoc. Biol. 80, 227-236.
185. Rose-John, S., and Schooltink, H. (2007). Cytokines are a therapeutic target for the prevention of inflammation-induced cancers. Recent Results Cancer Res. 174, 57-66.
186. Rudner, J., Elsaesser, S. J., Muller, A. C., Belka, C., and Jendrossek, V. (2010). Differential effects of anti-apoptotic Bcl-2 family members Mcl-1, Bcl2, and Bcl-xL on celecoxib-induced apoptosis. Biochem. Pharmacol. 79, 10-20.
187. Sakoguchi-Okada, N., Takahashi Yanaga, F., Fukada, K., Shiraishi, F., Taba, Y., Miwa, Y., Morimoto, S., Iida, M., and Sasaguri, T. (2007). Celecoxib inhibits the expression of survivin via the suppression of promoter activity in human colon cancer cells. Biochem. Pharmacol. 73, 1318-1329.
188. Sandau, K. B., Faus, H. G., and Brune, B. (2000). Induction of hypoxiainducible-factor 1 by nitric oxide is mediated via the PI 3K pathway. Biochem. Biophys. Res. Commun. 278, 263-267.
189. Sansone, P., Piazzi, G., Paterini, P., Strillacci, A., Ceccarelli, C., Minni, F., Biasco, G., Chieco, P., and Bonafe, M. (2009). Cyclooxygenase-2/carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells. J. Cell.Mol.Med.13, 3876-3887.
190. Sawa, T., and Ohshima, H. (2006). Nitrative DNA damage in inflammation and its possible role in carcinogenesis. Nitric Oxide 14, 91-100.
191. Schulze, J., Albers, J., Baranowsky, A., Keller, J., Spiro, A., Streichert, T., Zustin, J., Amling, M., and Schinke, T. (2010). Osteolytic prostate cancer cells induce the expression of specific cytokines in bone-forming osteoblasts through a Stat3/5-dependent mechanism. Bone 46, 524-533.
192. Schwarz, R. E., Vujanovic, N. L., and Hiserodt, J. C. (1989). Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic. Cancer Res. 49, 1441-1446.
193. Shamovsky, I., and Nudler, E. (2008). New insights into the mechanism of heat shock response activation. Cell. Mol. Life Sci. 65, 855-861.
194. Shchors, K., Shchors, E., Rostker, F., Lawlor, E. R., Brown-Swigart, L., and Evan, G. I. (2006). The Mycdependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev. 20, 2527-2538.
195. Shimizu, M., Deguchi, A., Lim, J. T., Moriwaki, H., Kopelovich, L., and Weinstein, I. B. (2005). (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin. Cancer Res. 11, 2735-2746.
196. Shin, B. K., Wang, H., Yim, A. M., Le Naour, F., Brichory, F., Jang, J. H., Zhao, R., Puravs, E., Tra, J., Michael, C. W., Misek, D. E., and Hanash, S. M. (2003). Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J. Biol. Chem. 278, 7607-7616.
197. Shinriki, S., Jono, H., Ota, K., Ueda, M., Kudo, M., Ota, T., Oike,Y., Endo, M., Ibusuki, M., Hiraki, A., Nakayama, H., Yoshitake, Y., Shinohara, M., and Ando, Y. (2009). Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin. Cancer Res. 15, 5426-5434.
198. Shirode, A. B., and Sylvester, P. W. (2010). Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling. Biomed. Pharmacother. 64, 327-332.
199. Siddiqui, I. A., Malik, A., Adhami, V. M., Asim, M., Hafeez, B. B., Sarfaraz, S., and Mukhtar, H. (2008). Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene 27, 2055-2063.
200. Singh, R., Wang, B., Shirvaikar, A., Khan, S., Kamat, S., Schelling, J. R., Konieczkowski, M., and Sedor, J. R. (1999). The IL-1 receptor and Rho directly associate to drive cell activation in inflammation. J. Clin. Invest. 103, 1561-1570.
201. Smolen, J. S., Avila, J. C., and Aletaha, D. (2011). Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction. Ann. Rheum. Dis. doi: 10.1136/annrheumdis2011-200395. [Epub ahead of print].
202. Solomon, S. D., Wittes, J., Finn, P. V., Fowler, R., Viner, J., Bertagnolli, M. M., Arber, N., Levin, B., Meinert, C. L., Martin, B., Pater, J. L., Goss, P. E., Lance, P., Obara, S., Chew, E. Y., Kim, J., Arndt, G., and Hawk, E. (2008). Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 117, 2104-2113.
203. Sparmann, A., and Bar-Sagi, D. (2004). Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6, 447-458.
204. Spektor, G., and Fuster, V. (2005). Drug insight: cyclo-oxygenase 2 inhibitors and cardiovascular risk-where are we now? Nat. Clin. Pract. Cardiovasc. Med. 2, 290-300.
205. Stangl, S., Gehrmann, M., Riegger, J., Kuhs, K., Riederer, I., Sievert, W., Hube, K., Mocikat, R., Dressel, R., Kremmer, E., Pockley, A.G., Friedrich, L., Vigh, L., Skerra, A., and Multhoff, G. (2011). Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc. Natl.Acad. Sci. U.S.A. 108, 733-738.
206. Stangl, S., Wortmann, A., Guertler, U., and Multhoff, G. (2006). Control of metastasized pancreatic carcinomas in SCID/beige mice with human IL-2/TKD-activated NK cells. J. Immunol. 176, 6270-6276.
207. Stock, A., Booth, S., and Cerundolo, V. (2011). Prostaglandin E2 suppresses the differentiation of retinoic acidproducing dendritic cells in mice and humans. J. Exp. Med. 208, 761-773.
208. Suganuma, M., Saha, A., and Fujiki, H. (2011). New cancer treatment strategy using combination of green tea catechins and anticancer drugs. Cancer Sci. 102, 317-323.
209. Sun, S. G., Lau, Y. S., Itonaga, I., Sabokbar, A., and Athanasou, N. A. (2006). Bone stromal cells in pagetic bone and Paget's sarcoma express RANKL and support human osteoclast formation. J. Pathol. 209, 114-120.
210. Surh, Y. J., Chun, K. S., Cha, H. H., Han, S. S., Keum, Y. S., Park, K. K., and Lee, S. S. (2001). Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat. Res. 480-481, 243-268.
211. Sutton,C.,Brereton,C.,Keogh,B.,Mills, K. H., and Lavelle, E. C. (2006). A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203, 1685-1691.
212. Takahashi, T., Uehara, H., Bando,Y., and Izumi, K. (2008). Soluble EP2 neutralizes prostaglandin E2-induced cell signaling and inhibits osteolytic tumor growth. Mol. Cancer Ther. 7, 2807-2816.
213. Taketomi, A., Takenaka, K., Matsumata,T.,Shimada,M.,Higashi,H., Shirabe, K., Itasaka, H., Adachi, E., Maeda,T.,and Sugimachi,K. (1997). Circulating intercellular adhesion molecule-1 in patients with hepatocellular carcinoma before and after hepatic resection. Hepatogastroenterology 44, 477-483.
214. Tang, Z. N., Zhang, F., Tang, P., Qi, X. W., and Jiang, J. (2011). Hypoxia induces RANK and RANKL expression by activating HIF-1alpha in breast cancer cells. Biochem. Biophys. Res. Commun. 408, 411-416.
215. Teitelbaum, S. L. (2000). Bone resorption by osteoclasts. Science 289, 1504-1508.
216. Thiery, J. P., Acloque, H., Huang, R. Y., and Nieto, M. A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890.
217. Tjiu, J. W., Liao, Y. H., Lin, S. J., Huang, Y. L., Tsai, W. L., Chu, C. Y., Kuo, M. L., and Jee, S. H. (2006). Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis. J. Invest. Dermatol. 126, 1143-1151.
218. Trelle, S., Reichenbach, S., Wandel, S., Hildebrand, P., Tschannen, B., Villiger, P. M., Egger, M., and Juni, P. (2011). Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 342, c7086.
219. Triantafilou, M., and Triantafilou, K. (2004). Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem. Soc. Trans. 32, 636-639.
220. Tseng, W. W., Deganutti, A., Chen, M. N., Saxton, R. E., and Liu, C. D. (2002). Selective cyclooxygenase-2 inhibitor rofecoxib (Vioxx) induces expression of cell cycle arrest genes and slows tumor growth in human pancreatic cancer. J. Gastrointest. Surg. 6, 838-843.
221. Vallabhapurapu, S., and Karin, M. (2009). Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27, 693-733.
222. Virchow, R. (1863). Die krankhaften Geschwülste. Berlin: August Hirschwald.
223. Voronov, E., Carmi, Y., and Apte, R. N. (2007). Role of IL-1-mediated inflammation in tumor angiogenesis. Adv. Exp. Med. Biol. 601, 265-270.
224. Vujanovic, N. L., Yasumura, S., Hirabayashi, H., Lin, W. C., Watkins, S., Herberman, R. B., and Whiteside, T. L. (1995). Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues. J. Immunol. 154, 281-289.
225. Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J., and Chen, Z. J. (2001). TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351.
226. Wang, L., Yi, T., Kortylewski, M., Pardoll, D. M., Zeng, D., and Yu, H. (2009a). IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J. Exp. Med. 206, 1457-1464.
227. Wang, S., Liu, Q., Zhang, Y., Liu, K., Yu, P., Liu, K., Luan, J., Duan, H., Lu, Z., Wang, F., Wu, E., Yagasaki, K., and Zhang, G. (2009b). Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action. Mol. Cancer 8, 81.
228. Watters, T. M., Kenny, E. F., and O'Neill, L. A. (2007). Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. Immunol. Cell Biol. 85, 411-419.
229. Weaver, C. T., Hawrylowicz, C. M., and Unanue, E. R. (1988). T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc. Natl. Acad. Sci. U.S.A. 85, 8181-8185.
230. Wei, D., Wang, L., He, Y., Xiong, H. Q., Abbruzzese, J. L., and Xie, K. (2004). Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity. Cancer Res. 64, 2030-2038.
231. Weichert, W., Boehm, M., Gekeler, V., Bahra, M., Langrehr, J., Neuhaus, P., Denkert, C., Imre, G., Weller, C., Hofmann,H. P., Niesporek, S.,Jacob, J., Dietel, M., Scheidereit, C., and Kristiansen, G. (2007). High expression of RelA/p65 is associated with activation of nuclear factor-kappaBdependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br. J. Cancer 97, 523-530.
232. Weiss, T. W., Simak, R., Kaun, C., Rega, G., Pfluger, H., Maurer, G., Huber, K., and Wojta, J. (2011). Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo. Anticancer Res. 31, 3273-3278.
233. Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., and Cao, Z. (1997a). MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7, 837-847.
234. Wesche, H., Korherr, C., Kracht, M., Falk, W., Resch, K., and Martin, M. U. (1997b). The interleukin-1 receptor accessory protein (IL-1RAcP) is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases). J. Biol. Chem. 272, 7727-7731.
235. Wheeler, D. S., Chase, M. A., Senft, A. P., Poynter, S. E., Wong, H. R., and Page, K. (2009). Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Tolllike receptor (TLR)-4. Respir. Res. 10, 31.
236. Whiteside, T. L., Vujanovic, N. L., and Herberman, R. B. (1998). Natural killer cells and tumor therapy. Curr. Top. Microbiol. Immunol. 230, 221-244.
237. Wilson, K. T., Fu, S., Ramanujam, K. S., and Meltzer, S. J. (1998). Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res. 58, 2929-2934.
238. Wink,D. A.,Vodovotz,Y.,Laval,J.,Laval, F., Dewhirst, M. W., and Mitchell, J. B. (1998). The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19, 711-721.
239. Wu, S., Rhee, K. J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H. R., Huso, D. L., Brancati, F. L., Wick, E., McAllister, F., Housseau, F., Pardoll, D. M., and Sears, C. L. (2009). A human colonic commensal promotes colon tumorigenesis via acti-vationofThelpertype17Tcell responses. Nat. Med. 15, 1016-1022.
240. Xiong, H. Q. (2004). Molecular targeting therapy for pancreatic cancer. Cancer Chemother. Pharmacol. 54(Suppl. 1), S69-S77.
241. Xu, X. F., Xie, C. G., Wang, X. P., Liu, J., Yu, Y. C., Hu, H. L., and Guo, C. Y. (2008). Selective inhibition of cyclooxygenase-2 suppresses the growth of pancreatic cancer cells in vitro and in vivo. Tohoku J. Exp. Med. 215, 149-157.
242. Yamada, T., Tsuda, M., Takahashi, T., Totsuka, Y., Shindoh, M., and Ohba, Y. (2011). RANKL expression specifically observed in vivo promotes epithelial mesenchymal transition and tumor progression. Am. J. Pathol. 178, 2845-2856.
243. Yamashita, M., Kurokawa, K., Sato, Y., Yamagata, A., Mimura, H., Yoshikawa, A., Sato, K., Nakano, A., and Fukai, S. (2010). Structural basis for the Rhoand phosphoinositidedependent localization of the exocyst subunit Sec3. Nat. Struct. Mol. Biol. 17, 180-186.
244. Yang, J., and Weinberg, R. A. (2008). Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell 14, 818-829.
245. Yasumura, S., Lin, W. C., Hirabayashi, H., Vujanovic, N. L., Herberman, R. B., and Whiteside, T. L. (1994). Immunotherapy of liver metastases of human gastric carcinoma with interleukin 2-activated natural killer cells. Cancer Res. 54, 3808-3816.
246. Yip-Schneider, M. T., Sweeney, C. J., Jung, S. H., Crowell, P. L., and Marshall, M. S. (2001). Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells. J. Pharmacol. Exp. Ther. 298, 976-985.
247. Yokota, S., Miyamae, T., Imagawa, T., Iwata, N., Katakura, S., and Mori, M. (2004). Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis. Mod. Rheumatol. 14, 12-17.
248. Yoshimatsu,K.,Altorki,N. K.,Golijanin, D., Zhang, F., Jakobsson, P. J., Dannenberg, A. J., and Subbaramaiah, K. (2001a). Inducible prostaglandin E synthase is overexpressed in nonsmall cell lung cancer. Clin. Cancer Res. 7, 2669-2674.
249. Yoshimatsu, K., Golijanin, D., Paty, P. B., Soslow, R. A., Jakobsson, P. J., DeLellis, R. A., Subbaramaiah, K., and Dannenberg, A. J. (2001b). Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin. Cancer Res. 7, 3971-3976.
250. Yu, H., Kortylewski, M., and Pardoll, D. (2007). Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 7, 41-51.
251. Yu, H., Pardoll, D., and Jove, R. (2009). STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer 9, 798-809.
252. Zeisberg, M., and Neilson, E. G. (2009). Biomarkers for epithelialmesenchymal transitions. J. Clin. Invest. 119, 1429-1437.
253. Zumsteg, A., and Christofori, G. (2009). Corrupt policemen: inflammatory cells promote tumor angiogenesis. Curr. Opin. Oncol. 21, 60-70.