Macrophage-tumor cell interactions regulate the function of nitric oxide

Frontiers in Physiology

Volumn 4 JUN, Issue , 2013, Pages

  Rahat, Michal A ^a   Hemmerlein, Bernhard ^b,c  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^c Helios Klinikum   (Germany)

Author keywords

Angiogenesis; Apoptosis; Inducible nitric oxide synthase (iNOS); Macrophage activation; Macrophage therapy; Macrophage induced death; Mir 146a; Tumor cells

Indexed keywords

ANGIOPOIETIN RECEPTOR; CYTOKINE; INDUCIBLE NITRIC OXIDE SYNTHASE; MATRIX METALLOPROTEINASE; MICRORNA 146A; NITRIC OXIDE; REACTIVE NITROGEN SPECIES; VASCULOTROPIN;

APOPTOSIS; BRAIN CANCER; BREAST CANCER; CANCER GRADING; CANCER INHIBITION; CANCER STAGING; CELL DEATH; CELL INTERACTION; CELL TRANSFORMATION; COLORECTAL CANCER; HEAD AND NECK CANCER; HUMAN; IMMUNE SYSTEM; LUNG NON SMALL CELL CANCER; MACROPHAGE; MACROPHAGE ACTIVATION; MELANOMA; METASTASIS; MOUTH CANCER; OVARY CANCER; OXYGEN TENSION; PANCREAS CANCER; REVIEW; STOMACH CANCER; TUMOR CELL; TUMOR GROWTH; TUMOR MICROENVIRONMENT; UTERINE CERVIX CANCER;

EID: 84884579194     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2013.00144     Document Type: Review

References (147)

1. Aktan, F. (2004). iNOS-mediated nitric oxide production and its regulation. Life Sci. 75, 639-653. doi: 10.1016/j.lfs.2003.10.042
2. Albina, J. E. (1995). On the expression of nitric oxide synthase by human macrophages. Why no NO? J. Leukoc. Biol. 58, 643-649.
3. Alderton, W. K., Cooper, C. E., and Knowles, R. G. (2001). Nitric oxide synthases: structure, function and inhibition. Biochem. J. 357, 593-615. doi: 10.1042/0264-6021:3570593
4. Allavena, P., Sica, A., Garlanda, C., and Mantovani, A. (2008). The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol. Rev. 222, 155-161. doi: 10.1111/j.1600-065X.2008.00607.x
5. Ambs, S., and Glynn, S. A. (2011). Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer. Cell Cycle 10, 619-624. doi: 10.4161/cc.10.41.4864
6. Andreesen, R., Hennemann, B., and Krause, S. W. (1998). Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale, current status, and perspectives. J. Leukoc. Biol. 64, 419-426.
7. Anttila, M. A., Voutilainen, K., Merivalo, S., Saarikoski, S., and Kosma, V. M. (2007). Prognostic significance of iNOS in epithelial ovarian cancer. Gynecol. Oncol. 105, 97-103. doi: 10.1016/j.ygyno.2006.10.049
8. Black, S. M., Devol, J. M., and Wedgwood, S. (2008). Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation. Am. J. Physiol. Cell Physiol. 294, C345-C354. doi: 10.1152/ajpcell.00216.2007
9. Bronte, V. (2009). Myeloid-derived suppressor cells in inflammation: uncovering cell subsets with enhanced immunosuppressive functions. Eur. J. Immunol. 39, 2670-2672. doi: 10.1002/eji.200939892
10. Brune, B. (2003). Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ. 10, 864-869. doi: 10.1038/sj.cdd.4401261
11. Bui, J. D., and Schreiber, R. D. (2007). Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr. Opin. Immunol. 19, 203-208. doi: 10.1016/j.coi.2007.02.001
12. Bulut, A. S., Erden, E., Sak, S. D., Doruk, H., Kursun, N., and Dincol, D. (2005). Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases. Virchows Arch. 447, 24-30. doi: 10.1007/s00428-005-1250-2
13. Chaiyarit, P., Ma, N., Hiraku, Y., Pinlaor, S., Yongvanit, P., Jintakanon, D., et al. (2005). Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis. Cancer Sci. 96, 553-559. doi: 10.1111/j.1349-7006.2005.00096.x
14. Chen, C. N., Hsieh, F. J., Cheng, Y. M., Chang, K. J., and Lee, P. H. (2006). Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer. J. Surg. Oncol. 94, 226-233. doi: 10.1002/jso.20372
15. Chen, H. H., Su, W. C., Chou, C. Y., Guo, H. R., Ho, S. Y., Que, J., et al. (2005). Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 63, 1093-1100. doi: 10.1016/j.ijrobp.2005.03.062
16. Chen, Y. K., Hsue, S. S., and Lin, L. M. (2002). Increased expression of inducible nitric oxide synthase for human buccal squamous-cell carcinomas: immunohistochemical, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR studies. Head Neck 24, 925-932. doi: 10.1002/hed.10131
17. Chowdhury, R., Godoy, L. C., Thiantanawat, A., Trudel, L. J., Deen, W. M., and Wogan, G. N. (2012). Nitric oxide produced endogenously is responsible for hypoxia-induced HIF-1alpha stabilization in colon carcinoma cells. Chem. Res. Toxicol. 25, 2194-2202. doi: 10.1021/tx300274a
18. Cianchi, F., Cortesini, C., Fantappie, O., Messerini, L., Sardi, I., Lasagna, N., et al. (2004). Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer. Clin. Cancer Res. 10, 2694-2704. doi: 10.1158/1078-0432.CCR-03-0192
19. Coffelt, S. B., Chen, Y. Y., Muthana, M., Welford, A. F., Tal, A. O., Scholz, A., et al. (2011). Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J. Immunol. 186, 4183-4190. doi: 10.4049/jimmunol.1002802
20. Coffelt, S. B., Hughes, R., and Lewis, C. E. (2009). Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim. Biophys. Acta 1796, 11-18.
21. Condeelis, J., and Pollard, J. W. (2006). Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263-266. doi: 10.1016/j.cell.2006.01.007
22. Corzo, C. A., Condamine, T., Lu, L., Cotter, M. J., Youn, J. I., Cheng, P., et al. (2010). HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 207, 2439-2453. doi: 10.1084/jem.20100587
23. Dai, R., Phillips, R. A., Zhang, Y., Khan, D., Crasta, O., and Ahmed, S. A. (2008). Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood 112, 4591-4597. doi: 10.1182/blood-2008-04-152488
24. Daniliuc, S., Bitterman, H., Rahat, M. A., Kinarty, A., Rosenzweig, D., and Lahat, N. (2003). Hypoxia inactivates inducible nitric oxide synthase in mouse macrophages by disrupting its interaction with alpha-actinin 4. J. Immunol. 171, 3225-3232.
25. De Palma, M., Murdoch, C., Venneri, M. A., Naldini, L., and Lewis, C. E. (2007). Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol. 28, 519-524. doi: 10.1016/j.it.2007.09.004
26. De Palma, M., Venneri, M. A., Galli, R., Sergi Sergi, L., Politi, L. S., Sampaolesi, M., et al. (2005). Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8, 211-226. doi: 10.1016/j.ccr.2005.08.002
27. De Vera, M. E., Shapiro, R. A., Nussler, A. K., Mudgett, J. S., Simmons, R. L., Morris, S. M., et al. (1996). Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc. Natl. Acad. Sci. U.S.A. 93, 1054-1059. doi: 10.1073/pnas.93.3.1054
28. Dinarello, C. A. (2006). The paradox of pro-inflammatory cytokines in cancer. Cancer Metastasis Rev. 25, 307-313. doi: 10.1007/s10555-006-9000-8
29. Dinarello, C. A. (2010). Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 29, 317-329. doi: 10.1007/s10555-010-9229-0
30. Donzelli, S., Switzer, C. H., Thomas, D. D., Ridnour, L. A., Espey, M. G., Isenberg, J. S., et al. (2006). The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: a new feature of nitrogen oxide signaling. Antioxid. Redox Signal. 8, 1363-1371. doi: 10.1089/ars.2006.8.1363
31. Dulak, J., and Jozkowicz, A. (2003). Regulation of vascular endothelial growth factor synthesis by nitric oxide: facts and controversies. Antioxid. Redox Signal. 5, 123-132. doi: 10.1089/152308603321223612
32. Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004). The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329-360. doi: 10.1146/annurev.immunol.22.012703.104803
33. Eggen, T., Sager, G., Arnes, M., Pettersen, I., and Orbo, A. (2011). Expression of iNOS-a favourable prognostic marker for early-stage carcinoma of the uterine cervix. Anticancer Res. 31, 2319-2325.
34. Eijan, A. M., Piccardo, I., Riveros, M. D., Sandes, E. O., Porcella, H., Jasnis, M. A., et al. (2002). Nitric oxide in patients with transitional bladder cancer. J. Surg. Oncol. 81, 203-208. doi: 10.1002/jso.10170
35. Ekmekcioglu, S., Ellerhorst, J. A., Prieto, V. G., Johnson, M. M., Broemeling, L. D., and Grimm, E. A. (2006). Tumor iNOS predicts poor survival for stage III melanoma patients. Int. J. Cancer 119, 861-866. doi: 10.1002/ijc.21767
36. Feng, C. W., Wang, L. D., Jiao, L. H., Liu, B., Zheng, S., and Xie, X. J. (2002). Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features. BMC Cancer 2:8. doi: 10.1186/1471-2407-2-8
37. Fitzpatrick, B., Mehibel, M., Cowen, R. L., and Stratford, I. J. (2008). iNOS as a therapeutic target for treatment of human tumors. Nitric Oxide 19, 217-224. doi: 10.1016/j.niox.2008.05.001
38. Franchi, A., Gallo, O., Paglierani, M., Sardi, I., Magnelli, L., Masini, E., et al. (2002). Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis. Head Neck 24, 16-23. doi: 10.1002/hed.10045
39. Franchi, A., Massi, D., Santucci, M., Masini, E., Rossi Degl'innocenti, D., Magnelli, L., et al. (2006). Inducible nitric oxide synthase activity correlates with lymphangiogenesis and vascular endothelial growth factor-C expression in head and neck squamous cell carcinoma. J. Pathol. 208, 439-445. doi: 10.1002/path.1892
40. Gabrilovich, D. I., and Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162-174. doi: 10.1038/nri2506
41. Giannopoulou, E., Ravazoula, P., Kalofonos, H., Makatsoris, T., and Kardamakis, D. (2006). Expression of HIF-1alpha and iNOS in astrocytic gliomas: a clinicopathological study. In Vivo 20, 421-425.
42. Glynn, S. A., Boersma, B. J., Dorsey, T. H., Yi, M., Yfantis, H. G., Ridnour, L. A., et al. (2010). Increased NOS2 predicts poor survival in estrogen receptor-negative breast cancer patients. J. Clin. Invest. 120, 3843-3854. doi: 10.1172/JCI42059
43. Gochman, E., Mahajna, J., Shenzer, P., Dahan, A., Blatt, A., Elyakim, R., et al. (2012). The expression of iNOS and nitrotyrosine in colitis and colon cancer in humans. Acta Histochem. 114, 827-835. doi: 10.1016/j.acthis.2012.02.004
44. Gordon, S., and Martinez, F. O. (2010). Alternative activation of macrophages: mechanism and functions. Immunity 32, 593-604. doi: 10.1016/j.immuni.2010.05.007
45. Goto, T., Haruma, K., Kitadai, Y., Ito, M., Yoshihara, M., Sumii, K., et al. (1999). Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients. Clin. Cancer Res. 5, 1411-1415.
46. Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674. doi: 10.1016/j.cell.2011.02.013
47. Hao, X. P., Pretlow, T. G., Rao, J. S., and Pretlow, T. P. (2001). Inducible nitric oxide synthase (iNOS) is expressed similarly in multiple aberrant crypt foci and colorectal tumors from the same patients. Cancer Res. 61, 419-422.
48. Hara, A., and Okayasu, I. (2004). Cyclooxygenase-2 and inducible nitric oxide synthase expression in human astrocytic gliomas: correlation with angiogenesis and prognostic significance. Acta Neuropathol. 108, 43-48. doi: 10.1007/s00401-004-0860-0
49. Heller, A. (2008). Apoptosis-inducing high (.)NO concentrations are not sustained either in nascent or in developed cancers. Chem. Med. Chem. 3, 1493-1499. doi: 10.1002/cmdc.200800257
50. Hennemann, B., Beckmann, G., Eichelmann, A., Rehm, A., and Andreesen, R. (1998). Phase I trial of adoptive immunotherapy of cancer patients using monocyte-derived macrophages activated with interferon gamma and lipopolysaccharide. Cancer Immunol. Immunother. 45, 250-256. doi: 10.1007/PL00006671
51. Hernandez, L., Smirnova, T., Kedrin, D., Wyckoff, J., Zhu, L., Stanley, E. R., et al. (2009). The EGF/CSF-1 paracrine invasion loop can be triggered by heregulin beta1 and CXCL12. Cancer Res. 69, 3221-3227. doi: 10.1158/0008-5472.CAN-08-2871
52. Hollborn, M., Stathopoulos, C., Steffen, A., Wiedemann, P., Kohen, L., and Bringmann, A. (2007). Positive feedback regulation between MMP-9 and VEGF in human RPE cells. Invest. Ophthalmol. Vis. Sci. 48, 4360-4367. doi: 10.1167/iovs.06-1234
53. Hussain, S. P., He, P., Subleski, J., Hofseth, L. J., Trivers, G. E., Mechanic, L., et al. (2008). Nitric oxide is a key component in inflammation-accelerated tumorigenesis. Cancer Res. 68, 7130-7136. doi: 10.1158/0008-5472.CAN-08-0410
54. Iyer, A. K., Azad, N., Wang, L., and Rojanasakul, Y. (2008). Role of S-nitrosylation in apoptosis resistance and carcinogenesis. Nitric Oxide 19, 146-151. doi: 10.1016/j.niox.2008.04.019
55. Jayaraman, P., Parikh, F., Lopez-Rivera, E., Hailemichael, Y., Clark, A., Ma, G., et al. (2012). Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J. Immunol. 188, 5365-5376. doi: 10.4049/jimmunol.1103553
56. Jayasurya, A., Dheen, S. T., Yap, W. M., Tan, N. G., Ng, Y. K., and Bay, B. H. (2003). Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer: correlation with outcome of patients after radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 56, 837-845. doi: 10.1016/S0360-3016(03)00122-6
57. Jeannin, J. F., Leon, L., Cortier, M., Sassi, N., Paul, C., and Bettaieb, A. (2008). Nitric oxide-induced resistance or sensitization to death in tumor cells. Nitric Oxide 19, 158-163. doi: 10.1016/j.niox.2008.04.024
58. Jia, W., Jackson-Cook, C., and Graf, M. R. (2010). Tumor-infiltrating, myeloid-derived suppressor cells inhibit T cell activity by nitric oxide production in an intracranial rat glioma + vaccination model. J. Neuroimmunol. 223, 20-30. doi: 10.1016/j.jneuroim.2010.03.011
59. Juang, S. H., Xie, K., Xu, L., Shi, Q., Wang, Y., Yoneda, J., et al. (1998). Suppression of tumorigenicity and metastasis of human renal carcinoma cells by infection with retroviral vectors harboring the murine inducible nitric oxide synthase gene. Hum. Gene Ther. 9, 845-854. doi: 10.1089/hum.1998.9.6-845
60. Kasper, H. U., Wolf, H., Drebber, U., Wolf, H. K., and Kern, M. A. (2004). Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma: correlation with microvessel density. World J. Gastroenterol. 10, 1918-1922.
61. Kees, T., and Egeblad, M. (2011). Innate immune cells in breast cancer-from villains to heroes? J. Mammary Gland Biol. Neoplasia 16, 189-203. doi: 10.1007/s10911-011-9224-2
62. Kimura, H., Weisz, A., Kurashima, Y., Hashimoto, K., Ogura, T., D'acquisto, F., et al. (2000). Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood 95, 189-197.
63. Kimura, H., Weisz, A., Ogura, T., Hitomi, Y., Kurashima, Y., Hashimoto, K., et al. (2001). Identification of hypoxia-inducible factor 1 ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia and nitric oxide. J. Biol. Chem. 276, 2292-2298.
64. Klimp, A. H., Hollema, H., Kempinga, C., Van Der Zee, A. G., De Vries, E. G., and Daemen, T. (2001). Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages. Cancer Res. 61, 7305-7309.
65. Koh, E., Noh, S. H., Lee, Y. D., Lee, H. Y., Han, J. W., Lee, H. W., et al. (1999). Differential expression of nitric oxide synthase in human stomach cancer. Cancer Lett. 146, 173-180. doi: 10.1016/S0304-3835(99)00265-7
66. Kong, G., Kim, E. K., Kim, W. S., Lee, K. T., Lee, Y. W., Lee, J. K., et al. (2002). Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer. J. Gastroenterol. Hepatol. 17, 914-921. doi: 10.1046/j.1440-1746.2002.02829.x
67. Kuncewicz, T., Balakrishnan, P., Snuggs, M. B., and Kone, B. C. (2001). Specific association of nitric oxide synthase-2 with Rac isoforms in activated murine macrophages. Am. J. Physiol. Renal Physiol. 281, F326-F336.
68. Kundu, J. K., and Surh, Y. J. (2008). Inflammation: gearing the journey to cancer. Mutat. Res. 659, 15-30. doi: 10.1016/j.mrrev.2008.03.002
69. Lahat, N., Bitterman, H., Engelmayer-Goren, M., Rosenzweig, D., Weiss-Cerem, L., and Rahat, M. A. (2011). Reduced TIMP-2 in hypoxia enhances angiogenesis. Am. J. Physiol. Cell Physiol. 300, C557-C566. doi: 10.1152/ajpcell.00177.2010
70. Lala, P. K., and Chakraborty, C. (2001). Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol. 2, 149-156. doi: 10.1016/S1470-2045(00)00256-4
71. Lancaster, J. R. Jr., and Xie, K. (2006). Tumors face NO problems? Cancer Res. 66, 6459-6462. doi: 10.1158/0008-5472.CAN-05-2900
72. Le, X., Wei, D., Huang, S., Lancaster, J. R. Jr., and Xie, K. (2005). Nitric oxide synthase II suppresses the growth and metastasis of human cancer regardless of its up-regulation of protumor factors. Proc. Natl. Acad. Sci. U.S.A. 102, 8758-8763. doi: 10.1073/pnas.0409581102
73. Lechner, M., Lirk, P., and Rieder, J. (2005). Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin. Cancer Biol. 15, 277-289. doi: 10.1016/j.semcancer.2005.04.004
74. Lee, T. W., Chen, G. G., Xu, H., Yip, J. H., Chak, E. C., Mok, T. S., et al. (2003). Differential expression of inducible nitric oxide synthase and peroxisome proliferator-activated receptor gamma in non-small cell lung carcinoma. Eur. J. Cancer 39, 1296-1301. doi: 10.1016/S0959-8049(02)00733-5
75. Lei, H., Ju, D. W., Yu, Y., Tao, Q., Chen, G., Gu, S., et al. (2000). Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma. Gene Ther. 7, 707-713. doi: 10.1038/sj.gt.3301162
76. Leon, L., Jeannin, J. F., and Bettaieb, A. (2008). Post-translational modifications induced by nitric oxide (NO): implication in cancer cells apoptosis. Nitric Oxide 19, 77-83. doi: 10.1016/j.niox.2008.04.014
77. Lewis, C. E., and Pollard, J. W. (2006). Distinct role of macrophages in different tumor microenvironments. Cancer Res. 66, 605-612. doi: 10.1158/0008-5472.CAN-05-4005
78. Li, L. G., and Xu, H. M. (2005). Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival. World J. Gastroenterol. 11, 2539-2544.
79. Lin, C. W., Shen, S. C., Ko, C. H., Lin, H. Y., and Chen, Y. C. (2010). Reciprocal activation of macrophages and breast carcinoma cells by nitric oxide and colony-stimulating factor-1. Carcinogenesis 31, 2039-2048. doi: 10.1093/carcin/bgq172
80. Lin, Z., Chen, S., Ye, C., and Zhu, S. (2003). Nitric oxide synthase expression in human bladder cancer and its relation to angiogenesis. Urol. Res. 31, 232-235. doi: 10.1007/s00240-003-0302-9
81. Lo, H. W., Hsu, S. C., Ali-Seyed, M., Gunduz, M., Xia, W., Wei, Y., et al. (2005). Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 7, 575-589. doi: 10.1016/j.ccr.2005.05.007
82. Ma, N., Tagawa, T., Hiraku, Y., Murata, M., Ding, X., and Kawanishi, S. (2006). 8-Nitroguanine formation in oral leukoplakia, a premalignant lesion. Nitric Oxide 14, 137-143. doi: 10.1016/j.niox.2005.09.012
83. Mantovani, A., Allavena, P., Sica, A., and Balkwill, F. (2008). Cancer-related inflammation. Nature 454, 436-444. doi: 10.1038/nature07205
84. Martinez, F. O., Helming, L., and Gordon, S. (2009). Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27, 451-483. doi: 10.1146/annurev.immunol.021908.132532
85. Massi, D., Franchi, A., Sardi, I., Magnelli, L., Paglierani, M., Borgognoni, L., et al. (2001). Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions. J. Pathol. 194, 194-200. doi: 10.1002/1096-9896(200106)194:2<194::AID-PATH851>3.0.CO;2-S
86. Mazibrada, J., Ritta, M., Mondini, M., De Andrea, M., Azzimonti, B., Borgogna, C., et al. (2008). Interaction between inflammation and angiogenesis during different stages of cervical carcinogenesis. Gynecol. Oncol. 108, 112-120. doi: 10.1016/j.ygyno.2007.08.095
87. Melillo, G., Taylor, L. S., Brooks, A., Cox, G. W., and Varesio, L. (1996). Regulation of inducible nitric oxide synthase expression in IFN-gamma-treated murine macrophages cultured under hypoxic conditions. J. Immunol. 157, 2638-2644.
88. Monnet, I., Breau, J. L., Moro, D., Lena, H., Eymard, J. C., Menard, O., et al. (2002). Intrapleural infusion of activated macrophages and gamma-interferon in malignant pleural mesothelioma: a phase II study. Chest 121, 1921-1927. doi: 10.1378/chest.121.6.1921
89. Moochhala, S., Chhatwal, V. J., Chan, S. T., Ngoi, S. S., Chia, Y. W., and Rauff, A. (1996). Nitric oxide synthase activity and expression in human colorectal cancer. Carcinogenesis 17, 1171-1174. doi: 10.1093/carcin/17.5.1171
90. Mosser, D. M. (2003). The many faces of macrophage activation. J. Leukoc. Biol. 73, 209-212. doi: 10.1189/jlb.0602325
91. Mosser, D. M., and Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958-969. doi: 10.1038/nri2448
92. Mosser, D. M., and Zhang, X. (2008). Activation of murine macrophages. Curr. Protoc. Immunol. Chapter 14:Unit 14.12. doi: 10.1002/0471142735.im1402s83
93. Murdoch, C., Giannoudis, A., and Lewis, C. E. (2004). Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104, 2224-2234. doi: 10.1182/blood-2004-03-1109
94. Murdoch, C., Muthana, M., Coffelt, S. B., and Lewis, C. E. (2008). The role of myeloid cells in the promotion of tumour angiogenesis. Nat. Rev. Cancer 8, 618-631. doi: 10.1038/nrc2444
95. Nagaraj, S., and Gabrilovich, D. I. (2008). Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res. 68, 2561-2563. doi: 10.1158/0008-5472.CAN-07-6229
96. Nagaraj, S., Gupta, K., Pisarev, V., Kinarsky, L., Sherman, S., Kang, L., et al. (2007). Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med. 13, 828-835. doi: 10.1038/nm1609
97. Nizet, V., and Johnson, R. S. (2009). Interdependence of hypoxic and innate immune responses. Nat. Rev. Immunol. 9, 609-617. doi: 10.1038/nri2607
98. Nomelini, R. S., De Abreu Ribeiro, L. C., Tavares-Murta, B. M., Adad, S. J., and Murta, E. F. (2008). Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors. Mediators Inflamm. 2008:186584. doi: 10.1155/2008/186584
99. Ohta, T., Takahashi, M., and Ochiai, A. (2006). Increased protein expression of both inducible nitric oxide synthase and cyclooxygenase-2 in human colon cancers. Cancer Lett. 239, 246-253. doi: 10.1016/j.canlet.2005.08.014
100. Oka, K., Suzuki, Y., Iida, H., and Nakano, T. (2003). Pd-ECGF positivity correlates with better survival, while iNOS has no predictive value for cervical carcinomas treated with radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 57, 217-221. doi: 10.1016/S0360-3016(03)00436-X
101. Oronsky, B. T., Knox, S. J., and Scicinski, J. J. (2012). Is nitric oxide (NO) the last word in radiosensitization? a review. Transl. Oncol. 5, 66-71.
102. Ostrand-Rosenberg, S., and Sinha, P. (2009). Myeloid-derived suppressor cells: linking inflammation and cancer. J. Immunol. 182, 4499-4506. doi: 10.4049/jimmunol.0802740
103. Ou Yang, K. X., Liang, J., and Huang, Z. Q. (2011). Association of clinicopathologic parameters with the expression of inducible nitric oxide synthase and vascular endothelial growth factor in mucoepidermoid carcinoma. Oral. Dis. 17, 590-596. doi: 10.1111/j.1601-0825.2011.01813.x
104. Ozel, E., Pestereli, H. E., Simsek, T., Erdogan, G., and Karaveli, F. S. (2006). Expression of cyclooxygenase-2 and inducible nitric oxide synthase in ovarian surface epithelial carcinomas: is there any correlation with angiogenesis or clinicopathologic parameters? Int. J. Gynecol. Cancer 16, 549-555. doi: 10.1111/j.1525-1438.2006.00567.x
105. Pautz, A., Art, J., Hahn, S., Nowag, S., Voss, C., and Kleinert, H. (2010). Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23, 75-93. doi: 10.1016/j.niox.2010.04.007
106. Perske, C., Lahat, N., Levin, S. S., Bitterman, H., Hemmerlein, B., and Rahat, M. A. (2010). Loss of inducible nitric oxide synthase expression in the mouse renal cell carcinoma cell line RENCA is mediated by microRNA miR-146a. Am. J. Pathol. 177, 2046-2054. doi: 10.2353/ajpath.2010.091111
107. Pucci, F., Venneri, M. A., Biziato, D., Nonis, A., Moi, D., Sica, A., et al. (2009). A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships. Blood 114, 901-914. doi: 10.1182/blood-2009-01-200931
108. Puhakka, A., Kinnula, V., Napankangas, U., Saily, M., Koistinen, P., Paakko, P., et al. (2003). High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma. APMIS 111, 1137-1146. doi: 10.1111/j.1600-0463.2003.apm1111210.x
109. Pukkila, M. J., Kellokoski, J. K., Virtaniemi, J. A., Kumpulainen, E. J., Johansson, R. T., Halonen, P. M., et al. (2002). Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression, clinicopathological data, and survival. Laryngoscope 112, 1084-1088. doi: 10.1097/00005537-200206000-00027
110. Qian, B. Z., and Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51. doi: 10.1016/j.cell.2010.03.014
111. Rabinovich, G. A., Gabrilovich, D., and Sotomayor, E. M. (2007). Immunosuppressive strategies that are mediated by tumor cells. Annu. Rev. Immunol. 25, 267-296. doi: 10.1146/annurev.immunol.25.022106.141609
112. Radi, R. (2004). Nitric oxide, oxidants, and protein tyrosine nitration. Proc. Natl. Acad. Sci. U.S.A. 101, 4003-4008. doi: 10.1073/pnas.0307446101
113. Rahat, M. A., Bitterman, H., and Lahat, N. (2011). Molecular mechanisms regulating macrophage response to hypoxia. Front. Immunol. 2:45. doi: 10.3389/fimmu.2011.00045
114. Rajnakova, A., Moochhala, S., Goh, P. M., and Ngoi, S. (2001). Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer. Cancer Lett. 172, 177-185. doi: 10.1016/S0304-3835(01)00645-0
115. Ratovitski, E. A., Alam, M. R., Quick, R. A., McMillan, A., Bao, C., Kozlovsky, C., et al. (1999a). Kalirin inhibition of inducible nitric-oxide synthase. J. Biol. Chem. 274, 993-999.
116. Ratovitski, E. A., Bao, C., Quick, R. A., Mcmillan, A., Kozlovsky, C., and Lowenstein, C. J. (1999b). An inducible nitric-oxide synthase (NOS)-associated protein inhibits NOS dimerization and activity. J. Biol. Chem. 274, 30250-30257.
117. Reiman, J. M., Kmieciak, M., Manjili, M. H., and Knutson, K. L. (2007). Tumor immunoediting and immunosculpting pathways to cancer progression. Semin. Cancer Biol. 17, 275-287. doi: 10.1016/j.semcancer.2007.06.009
118. Ridnour, L. A., Isenberg, J. S., Espey, M. G., Thomas, D. D., Roberts, D. D., and Wink, D. A. (2005). Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc. Natl. Acad. Sci. U.S.A. 102, 13147-13152. doi: 10.1073/pnas.0502979102
119. Ridnour, L. A., Thomas, D. D., Donzelli, S., Espey, M. G., Roberts, D. D., Wink, D. A., et al. (2006). The biphasic nature of nitric oxide responses in tumor biology. Antioxid. Redox Signal. 8, 1329-1337. doi: 10.1089/ars.2006.8.1329
120. Ridnour, L. A., Windhausen, A. N., Isenberg, J. S., Yeung, N., Thomas, D. D., Vitek, M. P., et al. (2007). Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways. Proc. Natl. Acad. Sci. U.S.A. 104, 16898-16903. doi: 10.1073/pnas.0702761104
121. Ropponen, K. M., Kellokoski, J. K., Lipponen, P. K., Eskelinen, M. J., Alanne, L., Alhava, E. M., et al. (2000). Expression of inducible nitric oxide synthase in colorectal cancer and its association with prognosis. Scand. J. Gastroenterol. 35, 1204-1211. doi: 10.1080/003655200750056709
122. Sandes, E. O., Faletti, A. G., Riveros, M. D., Vidal Mdel, C., Gimenez, L., Casabe, A. R., et al. (2005). Expression of inducible nitric oxide synthase in tumoral and non-tumoral epithelia from bladder cancer patients. Nitric Oxide 12, 39-45. doi: 10.1016/j.niox.2004.11.003
123. Schreiber, R. D., Old, L. J., and Smyth, M. J. (2011). Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331, 1565-1570. doi: 10.1126/science.1203486
124. Stout, R. D., and Suttles, J. (2004). Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J. Leukoc. Biol. 76, 509-513. doi: 10.1189/jlb.0504272
125. Stout, R. D., Watkins, S. K., and Suttles, J. (2009). Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages. J. Leukoc. Biol. 86, 1105-1109. doi: 10.1189/jlb.0209073
126. Swana, H. S., Smith, S. D., Perrotta, P. L., Saito, N., Wheeler, M. A., and Weiss, R. M. (1999). Inducible nitric oxide synthase with transitional cell carcinoma of the bladder. J. Urol. 161, 630-634. doi: 10.1016/S0022-5347(01)61985-2
127. Switzer, C. H., Glynn, S. A., Cheng, R. Y., Ridnour, L. A., Green, J. E., Ambs, S., et al. (2012). S-Nitrosylation of EGFR and src activates an oncogenic signaling network in human basal-like breast cancer. Mol. Cancer Res. 10, 1203-1215. doi: 10.1158/1541-7786.MCR-12-0124
128. Taylor, B. S., De Vera, M. E., Ganster, R. W., Wang, Q., Shapiro, R. A., Morris, S. M. Jr., et al. (1998). Multiple NF-kappaB enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J. Biol. Chem. 273, 15148-15156. doi: 10.1074/jbc.273.24.15148
129. Tschugguel, W., Schneeberger, C., Unfried, G., Czerwenka, K., Weninger, W., Mildner, M., et al. (1999). Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade. Breast Cancer Res. Treat. 56, 145-151. doi: 10.1023/A:1006288526311
130. Vakkala, M., Kahlos, K., Lakari, E., Paakko, P., Kinnula, V., and Soini, Y. (2000). Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas. Clin. Cancer Res. 6, 2408-2416.
131. Venneri, M. A., De Palma, M., Ponzoni, M., Pucci, F., Scielzo, C., Zonari, E., et al. (2007). Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 109, 5276-5285. doi: 10.1182/blood-2006-10-053504
132. Vesely, M. D., Kershaw, M. H., Schreiber, R. D., and Smyth, M. J. (2011). Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 29, 235-271. doi: 10.1146/annurev-immunol-031210-101324
133. Vickers, S. M., Macmillan-Crow, L. A., Green, M., Ellis, C., and Thompson, J. A. (1999). Association of increased immunostaining for inducible nitric oxide synthase and nitrotyrosine with fibroblast growth factor transformation in pancreatic cancer. Arch. Surg. 134, 245-251. doi: 10.1001/archsurg.134.3.245
134. Walmsley, S. R., Chilvers, E. R., and Whyte, M. K. (2009). Hypoxia. Hypoxia, hypoxia inducible factor and myeloid cell function. Arthritis Res. Ther. 11, 219. doi: 10.1186/ar2632
135. Wang, B., Wei, D., Crum, V. E., Richardson, E. L., Xiong, H. H., Luo, Y., et al. (2003). A novel model system for studying the double-edged roles of nitric oxide production in pancreatic cancer growth and metastasis. Oncogene 22, 1771-1782. doi: 10.1038/sj.onc.1206386
136. Wang, X., Zhao, Q., Matta, R., Meng, X., Liu, X., Liu, C. G., et al. (2009). Inducible nitric-oxide synthase expression is regulated by mitogen-activated protein kinase phosphatase-1. J. Biol. Chem. 284, 27123-27134. doi: 10.1074/jbc.M109.051235
137. Weigert, A., and Brune, B. (2008). Nitric oxide, apoptosis and macrophage polarization during tumor progression. Nitric Oxide 19, 95-102. doi: 10.1016/j.niox.2008.04.021
138. Wink, D. A., Hines, H. B., Cheng, R. Y., Switzer, C. H., Flores-Santana, W., Vitek, M. P., et al. (2011). Nitric oxide and redox mechanisms in the immune response. J. Leukoc. Biol. 89, 873-891. doi: 10.1189/jlb.1010550
139. Wyckoff, J., Wang, W., Lin, E. Y., Wang, Y., Pixley, F., Stanley, E. R., et al. (2004). A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 64, 7022-7029. doi: 10.1158/0008-5472.CAN-04-1449
140. Xie, Q., and Nathan, C. (1994). The high-output nitric oxide pathway: role and regulation. J. Leukoc. Biol. 56, 576-582.
141. Yang, L., Guo, A., and Gu, J. C. (2011). c-Jun N-terminal kinase and nuclear factor kappaB mediate nitric oxide-induced expression of matrix metalloproteinase-13. Int. Orthop. 35, 1261-1266. doi: 10.1007/s00264-010-1056-y
142. Yasuda, H. (2008). Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer. Nitric Oxide 19, 205-216. doi: 10.1016/j.niox.2008.04.026
143. Ying, L., Hofseth, A. B., Browning, D. D., Nagarkatti, M., Nagarkatti, P. S., and Hofseth, L. J. (2007). Nitric oxide inactivates the retinoblastoma pathway in chronic inflammation. Cancer Res. 67, 9286-9293. doi: 10.1158/0008-5472.CAN-07-2238
144. Zafirellis, K., Zachaki, A., Agrogiannis, G., and Gravani, K. (2010). Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer. APMIS 118, 115-124. doi: 10.1111/j.1600-0463.2009.02569.x
145. Zhang, J., Peng, B., and Chen, X. (2005). Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin. Cancer Res. 11, 7334-7343. doi: 10.1158/1078-0432.CCR-05-0241
146. Zhang, W., He, X. J., Ma, Y. Y., Wang, H. J., Xia, Y. J., Zhao, Z. S., et al. (2011). Inducible nitric oxide synthase expression correlates with angiogenesis, lymphangiogenesis, and poor prognosis in gastric cancer patients. Hum. Pathol. 42, 1275-1282. doi: 10.1016/j.humpath.2010.09.020
147. Ziche, M., and Morbidelli, L. (2009). Molecular regulation of tumour angiogenesis by nitric oxide. Eur. Cytokine Netw. 20, 164-170.