The tumour microenvironment: A novel target for cancer therapy

Oral Diseases

Volumn 15, Issue 1, 2009, Pages 8-17

  Hanna, E ^a   Quick, J ^a,b   Libutti, S K ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Combination therapy; Endothelial cells; Extracellular matrix; Fibroblasts; Leucocytes; Tumour microenvironment

Indexed keywords

0118; 5 CHLORO 2,4 DIHYDROXYPYRIDINE PLUS OXONATE POTASSIUM PLUS TEGAFUR; 6 HYDROXYMETHYLACYLFULVENE; ALPHA INTERFERON; ANGINEX; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CANCER VACCINE; CAPECITABINE; CARBOPLATIN; CISPLATIN; CYCLOPHOSPHAMIDE; DOXORUBICIN; ENDOSTATIN; FLUOROURACIL; FRACTALKINE; GEMCITABINE; IMATINIB; INTERLEUKIN 15; INTERLEUKIN 18 BINDING PROTEIN; INTERLEUKIN 2; IROFULVEN; LENALIDOMIDE; MELPHALAN; MONOCLONAL ANTIBODY DC101; PACLITAXEL; SORAFENIB; STATHMIN; SUNITINIB; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CLINICAL TRIAL; COLORECTAL CANCER; COMBINATION CHEMOTHERAPY; DRUG MECHANISM; DRUG POTENCY; DRUG POTENTIATION; DRUG TARGETING; EXTRACELLULAR MATRIX; HEAD AND NECK CANCER; HUMAN; LIVER CELL CARCINOMA; LOW DRUG DOSE; MELANOMA; MONOTHERAPY; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; REVIEW; TUMOR VASCULARIZATION;

ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENDOTHELIAL CELLS; EXTRACELLULAR MATRIX; FIBROBLASTS; FORECASTING; HUMANS; LEUKOCYTES; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NEOPLASMS; PERICYTES;

EID: 57549092526     PISSN: 1354523X     EISSN: 16010825     Source Type: Journal    
DOI: 10.1111/j.1601-0825.2008.01471.x     Document Type: Review

References (127)

1. Abraham M, Shapiro S, Lahat N, Miller A (2002). The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells. Int Immunol 14 : 1449 1457.
2. Abraham D, Abri S, Hofmann M, Holtl W, Aharinejad S (2003). Low dose carboplatin combined with angiostatic agents prevents metastasis in human testicular germ cell tumor xenografts. J Urol 170 : 1388 1393.
3. Ahmad SA, Liu W, Jung YD et al (2001). The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer. Cancer Res 61 : 1255 1259.
4. Algire GH, Chalkley HW, Legallais FY, Park HD (1945). Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6 : 73 85.
5. Arap W, Pasqualini R, Ruoslahti E (1998). Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279 : 377 380.
6. Atula S, Grenman R, Syrjanen S (1997). Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro. Exp Cell Res 235 : 180 187.
7. Balza E, Mortara L, Sassi F et al (2006). Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin. Clin Cancer Res 12 : 2575 2582.
8. Barcellos-Hoff MH, Ravani SA (2000). Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 60 : 1254 1260.
9. Basak GW, Zapala L, Wysocki PJ, Mackiewicz A, Jakobisiak M, Lasek W (2008). Interleukin 15 augments antitumor activity of cytokine gene-modified melanoma cell vaccines in a murine model. Oncol Rep 19 : 1173 1179.
10. Bergers G, Song S (2005). The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7 : 452 464.
11. Bingle L, Brown NJ, Lewis CE (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196 : 254 265.
12. Blansfield JA, Caragacianu D, Alexander HR III. et al (2008). Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clin Cancer Res 14 : 270 280.
13. Blasi F (1999). The urokinase receptor. A cell surface, regulated chemokine. APMIS 107 : 96 101.
14. Blavier L, Lazaryev A, Dorey F, Shackleford GM, DeClerck YA (2006). Matrix metalloproteinases play an active role in Wnt1-induced mammary tumorigenesis. Cancer Res 66 : 2691 2699.
15. Boehm T, Folkman J, Browder T, O'Reilly MS (1997). Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390 : 404 407.
16. Brandwijk RJ, Dings RP, van der Linden E, Mayo KH, Thijssen VL, Griffioen AW (2006). Anti-angiogenesis and anti-tumor activity of recombinant anginex. Biochem Biophys Res Commun 349 : 1073 1078.
17. Browder T, Butterfield CE, Kraling BM et al (2000). Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60 : 1878 1886.
18. Bubenik J (1996). Cytokine gene-modified vaccines in the therapy of cancer. Pharmacol Ther 69 : 1 14.
19. Buerkle MA, Pahernik SA, Sutter A, Jonczyk A, Messmer K, Dellian M (2002). Inhibition of the alpha-nu integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo. Br J Cancer 86 : 788 795.
20. Chakraborty M, Abrams SI, Camphausen K et al (2003). Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy. J Immunol 170 : 6338 6347.
21. Coussens LM, Tinkle CL, Hanahan D, Werb Z (2000). MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103 : 481 490.
22. Crippa L, Gasparri A, Sacchi A, Ferrero E, Curnis F, Corti A (2008). Synergistic damage of tumor vessels with ultra low-dose endothelial-monocyte activating polypeptide-II and neovasculature-targeted tumor necrosis factor-alpha. Cancer Res 68 : 1154 1161.
23. Curnis F, Sacchi A, Corti A (2002). Improving chemotherapeutic drug penetration in tumors by vascular targeting and barrier alteration. J Clin Invest 110 : 475 482.
24. Derynck R, Akhurst RJ, Balmain A (2001). TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29 : 117 129.
25. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001). Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193 : 233 238.
26. Dings RP, Laar ES, Webber J et al (2008). Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven. Cancer Lett 265 : 270 280.
27. Dorrell MI, Aguilar E, Scheppke L, Barnett FH, Friedlander M (2007). Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc Natl Acad Sci USA 104 : 967 972.
28. Dudley ME, Wunderlich JR, Yang JC et al (2002). A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother 25 : 243 251.
29. Dudley ME, Wunderlich JR, Yang JC et al (2005). Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 23 : 2346 2357.
30. Dunbar SD, Ornstein DL, Zacharski LR (2000). Cancer treatment with inhibitors of urokinase-type plasminogen activator and plasmin. Expert Opin Investig Drugs 9 : 2085 2092.
31. Elia L, Aurisicchio L, Facciabene A et al (2007). CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge. Cancer Gene Ther 14 : 201 210.
32. Epardaud M, Elpek KG, Rubinstein MP et al (2008). Interleukin-15/ interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells. Cancer Res 68 : 2972 2983.
33. Escudier B, Pluzanska A, Koralewski P et al (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370 : 2103 2111.
34. Ferris RL, Whiteside TL, Ferrone S (2006). Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res 12 : 3890 3895.
35. Ferrone S, Whiteside TL (2007). Tumor microenvironment and immune escape. Surg Oncol Clin N Am 16 : 755 774.
36. Folkman J (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med 285 : 1182 1186.
37. Gabrilovich DI, Chen HL, Girgis KR et al (1996). Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2 : 1096 1103.
38. Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP (1999). Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 5 : 2963 2970.
39. Gao JQ, Kanagawa N, Xu DH et al (2008). Combination of two fiber-mutant adenovirus vectors, one encoding the chemokine FKN and another encoding cytokine interleukin 12, elicits notably enhanced anti-tumor responses. Cancer Immunol Immunother Epub ahead of print.
40. Gnant MF, Berger AC, Huang J et al (1999). Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus. Cancer Res 59 : 4668 4674.
41. Grover AC, Tangrea MA, Woodson KG et al (2006). Tumor-associated endothelial cells display GSTP1 and RARbeta2 promoter methylation in human prostate cancer. J Transl Med 4 : 13.
42. Halin C, Gafner V, Villani ME et al (2003). Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to interleukin 12 and to tumor necrosis factor alpha. Cancer Res 63 : 3202 3210.
43. Hanahan D, Bergers G, Bergsland E (2000). Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105 : 1045 1047.
44. Hanson JA, Gillespie JW, Grover A et al (2006). Gene promoter methylation in prostate tumor-associated stromal cells. J Natl Cancer Inst 98 : 255 261.
45. Hasumi Y, Klosowska-Wardega A, Furuhashi M, Ostman A, Heldin CH, Hellberg C (2007). Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signaling. Int J Cancer 121 : 2606 2614.
46. Hicklin DJ, Ellis LM (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23 : 1011 1027.
47. Hood JD, Bednarski M, Frausto R et al (2002). Tumor regression by targeted gene delivery to the neovasculature. Science 296 : 2404 2407.
48. van Horssen R, Ten Hagen TL, Eggermont AM (2006). TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 11 : 397 408.
49. Howe JR, Roth S, Ringold JC et al (1998). Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280 : 1086 1088.
50. Hurwitz H, Fehrenbacher L, Novotny W et al (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 : 2335 2342.
51. Jacoby RF, Schlack S, Sekhon G, Laxova R (1997). Del(10)(q22.3q24.1) associated with juvenile polyposis. Am J Med Genet 70 : 361 364.
52. Jeffes EW, Zhang JG, Hoa N et al (2005). Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma. J Immunol 174 : 2533 2543.
53. Jefford M, Maraskovsky E, Cebon J, Davis ID (2001). The use of dendritic cells in cancer therapy. Lancet Oncol 2 : 343 353.
54. Kao J, Houck K, Fan Y et al (1994). Characterization of a novel tumor-derived cytokine. Endothelial-monocyte activating polypeptide II. J Biol Chem 269 : 25106 25119.
55. Kerbel RS (1991). Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays 13 : 31 36.
56. Khong HT, Restifo NP (2002). Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol 3 : 999 1005.
57. Killeen S, Hennessey A, El Hassan Y, Waldron B (2008). The urokinase plasminogen activator system in cancer: a putative therapeutic target? Drug News Perspect 21 : 107 116.
58. Klebanoff CA, Finkelstein SE, Surman DR et al (2004). IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 101 : 1969 1974.
59. Kurozumi K, Hardcastle J, Thakur R et al (2007). Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy. J Natl Cancer Inst 99 : 1768 1781.
60. Lakka SS, Gondi CS, Yanamandra N et al (2003). Synergistic down-regulation of urokinase plasminogen activator receptor and matrix metalloproteinase-9 in SNB19 glioblastoma cells efficiently inhibits glioma cell invasion, angiogenesis, and tumor growth. Cancer Res 63 : 2454 2461.
61. Lans TE, de Wilt JH, van Geel AN, Eggermont AM (2002). Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable sSewart-Treves lymphangiosarcoma. Ann Surg Oncol 9 : 1004 1009.
62. Lawler J (2000). The functions of thrombospondin-1 and-2. Curr Opin Cell Biol 12 : 634 640.
63. Li J, Hu P, Khawli LA, Epstein AL (2003a). Complete regression of experimental solid tumors by combination LEC/chTNT-3 immunotherapy and CD25(+) T-cell depletion. Cancer Res 63 : 8384 8392.
64. Li J, Hu P, Khawli LA, Epstein AL (2003b). LEC/chTNT-3 fusion protein for the immunotherapy of experimental solid tumors. J Immunother 26 : 320 331.
65. Li J, Dong X, Xu Z et al (2008). Endostatin gene therapy enhances the efficacy of paclitaxel to suppress breast cancers and metastases in mice. J Biomed Sci 15 : 99 109.
66. Libutti SK, Paciotti GF, Myer L et al (2007). Preliminary results of a phase I clinical trial of CYT-6091: a pegylated colloidal gold-TNF nanomedicine. J Clin Oncol, 2007 ASCO Meeting Proceedings Part I. 25 : 3603.
67. Liu F, Tan G, Li J, Dong X, Krissansen GW, Sun X (2007). Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in mice. Cancer Sci 98 : 1381 1387.
68. Magzoub M, Jin S, Verkman AS (2008). Enhanced macromolecule diffusion deep in tumors after enzymatic digestion of extracellular matrix collagen and its associated proteoglycan decorin. FASEB J 22 : 276 284.
69. Manegold C (2008). Bevacizumab for the treatment of advanced non-small-cell lung cancer. Expert Rev Anticancer Ther 8 : 689 699.
70. Mangiameli DP, Blansfield JA, Kachala S et al (2007). Combination therapy targeting the tumor microenvironment is effective in a model of human ocular melanoma. J Transl Med 5 : 38.
71. Manning EA, Ullman JG, Leatherman JM et al (2007). A vascular endothelial growth factor receptor-2 inhibitor enhances antitumor immunity through an immune-based mechanism. Clin Cancer Res 13 : 3951 3959.
72. von Marschall Z, Scholz A, Cramer T et al (2003). Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 95 : 437 448.
73. Marshall E (2002). Cancer therapy. Setbacks for endostatin. Science 295 : 2198 2199.
74. Marvin MR, Libutti SK, Kayton M et al (1996). A novel tumor-derived mediator that sensitizes cytokine-resistant tumors to tumor necrosis factor. J Surg Res 63 : 248 255.
75. McCarty MF, Somcio RJ, Stoeltzing O et al (2007). Overexpression of PDGF-BB decreases colorectal and pancreatic cancer growth by increasing tumor pericyte content. J Clin Invest 117 : 2114 2122.
76. McMahon G (2000). VEGF receptor signaling in tumor angiogenesis. Oncologist 5 (Suppl. 1 3 10.
77. Miller KD, Sweeney CJ, Sledge GW Jr. (2001). Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol 19 : 1195 1206.
78. Miller KD, Chap LI, Holmes FA et al (2005). Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23 : 792 799.
79. Mistry SJ, Atweh GF (2006). Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer. Mol Cancer Ther 5 : 3248 3257.
80. Mistry SJ, Bank A, Atweh GF (2007). Synergistic antiangiogenic effects of stathmin inhibition and taxol exposure. Mol Cancer Res 5 : 773 782.
81. Miyamoto A, Umeshita K, Sakon M et al (2000). Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of alpha-interferon and oral tegafur/uracil. J Gastroenterol Hepatol 15 : 1447 1451.
82. Mizukami Y, Jo WS, Duerr EM et al (2005). Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med 11 : 992 997.
83. Mortara L, Balza E, Sassi F et al (2007). Therapy-induced antitumor vaccination by targeting tumor necrosis factor alpha to tumor vessels in combination with melphalan. Eur J Immunol 37 : 3381 3392.
84. Nagano H, Miyamoto A, Wada H et al (2007). Interferon-alpha and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk, and multiple nodules. Cancer 110 : 2493 2501.
85. Nagase H, Woessner JF Jr. (1999). Matrix metalloproteinases. J Biol Chem 274 : 21491 21494.
86. Netti PA, Berk DA, Swartz MA, Grodzinsky AJ, Jain RK (2000). Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res 60 : 2497 2503.
87. Nyberg P, Xie L, Kalluri R (2005). Endogenous inhibitors of angiogenesis. Cancer Res 65 : 3967 3979.
88. Ohmura Y, Yoshikawa K, Saga S, Ueda R, Kazaoka Y, Yamada S (2008). Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy. Oncol Rep 19 : 1265 1270.
89. Ohta M, Tanaka F, Yamaguchi H, Sadanaga N, Inoue H, Mori M (2005). The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. Int J Oncol 26 : 41 47.
90. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999). Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59 : 5002 5011.
91. Ooyama A, Oka T, Zhao HY, Yamamoto M, Akiyama SI, Fukushima M (2008). Anti-angiogenic effect of 5-Fluorouracil-based drugs against human colon cancer xenografts. Cancer Lett 267 : 26 36.
92. Osada T, Chong G, Tansik R et al (2008). The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer Immunol Immunother 57 : 1115 1124.
93. Ota H, Nagano H, Sakon M et al (2005). Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression. Br J Cancer 93 : 557 564.
94. Paget S (1889). he distribution of secondary growths in cancer of the breast. Lancet 1 : 571 573.
95. Parmiani G, Rivoltini L, Andreola G, Carrabba M (2000). Cytokines in cancer therapy. Immunol Lett 74 : 41 44.
96. Pietras K, Pahler J, Bergers G, Hanahan D (2008). Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 5 : e19.
97. Plum SM, Hanson AD, Volker KM et al (2003). Synergistic activity of recombinant human endostatin in combination with adriamycin: analysis of in vitro activity on endothelial cells and in vivo tumor progression in an orthotopic murine mammary carcinoma model. Clin Cancer Res 9 : 4619 4626.
98. Rodriguez-Canales J, Hanson JC, Tangrea MA et al (2007). Identification of a unique epigenetic sub-microenvironment in prostate cancer. J Pathol 211 : 410 419.
99. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME (2008). Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8 : 299 308.
100. Sacchi A, Gasparri A, Curnis F, Bellone M, Corti A (2004). Crucial role for interferon gamma in the synergism between tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) and doxorubicin. Cancer Res 64 : 7150 7155.
101. Sacchi A, Gasparri A, Gallo-Stampino C, Toma S, Curnis F, Corti A (2006). Synergistic antitumor activity of cisplatin, paclitaxel, and gemcitabine with tumor vasculature-targeted tumor necrosis factor-alpha. Clin Cancer Res 12 : 175 182.
102. Sakon M, Nagano H, Dono K et al (2002). Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches. Cancer 94 : 435 442.
103. Sandler A, Gray R, Perry MC et al (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355 : 2542 2550.
104. Sarmiento R, Gasparini G (2008). Antiangiogenic metronomic chemotherapy. Onkologie 31 : 161 162.
105. Seiwert TY, Haraf DJ, Cohen EE et al (2008). Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol 26 : 1732 1741.
106. Shapiro SD (1998). Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol 10 : 602 608.
107. Shekhar MP, Werdell J, Santner SJ, Pauley RJ, Tait L (2001). Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. Cancer Res 61 : 1320 1326.
108. Shojaei F, Ferrara N (2007). Antiangiogenic therapy for cancer: an update. Cancer J 13 : 345 348.
109. Sica A, Bronte V (2007). Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117 : 1155 1166.
110. Singh H, Serrano LM, Pfeiffer T et al (2007). Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. Cancer Res 67 : 2872 2880.
111. Steeghs N, Nortier JW, Gelderblom H (2007). Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol 14 : 942 953.
112. Sternlicht MD, Lochter A, Sympson CJ et al (1999). The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98 : 137 146.
113. Stoklasek TA, Schluns KS, Lefrancois L (2006). Combined IL-15/IL-15Ralpha immunotherapy maximizes IL-15 activity in vivo. J Immunol 177 : 6072 6080.
114. Tangrea MA, Chuaqui RF, Gillespie JW et al (2004). Expression microdissection: operator-independent retrieval of cells for molecular profiling. Diagn Mol Pathol 13 : 207 212.
115. Tohnya TM, Ng SS, Dahut WL et al (2004). A phase I study of oral CC-5013 (lenalidomide, Revlimid), a thalidomide derivative, in patients with refractory metastatic cancer. Clin Prostate Cancer 2 : 241 243.
116. Wada H, Nagano H, Yamamoto H et al (2007). Combination therapy of interferon-alpha and 5-fluorouracil inhibits tumor angiogenesis in human hepatocellular carcinoma cells by regulating vascular endothelial growth factor and angiopoietins. Oncol Rep 18 : 801 809.
117. Westermarck J, Kahari VM (1999). Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13 : 781 792.
118. Willhauck MJ, Mirancea N, Vosseler S et al (2007). Reversion of tumor phenotype in surface transplants of skin SCC cells by scaffold-induced stroma modulation. Carcinogenesis 28 : 595 610.
119. Wu PC, Alexander HR, Huang J et al (1999). In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII). Cancer Res 59 : 205 212.
120. Wu MP, Young MJ, Tzeng CC et al (2008). A novel role of thrombospondin-1 in cervical carcinogenesis: Inhibit stroma reaction by inhibiting activated fibroblasts from invading cancer. Carcinogenesis 29 : 1115 1123.
121. Yang JC (2004). Bevacizumab for patients with metastatic renal cancer: an update. Clin Cancer Res 10 : 6367S 6370S.
122. Yang H, Grossniklaus HE (2006). Combined immunologic and anti-angiogenic therapy reduces hepatic micrometastases in a murine ocular melanoma model. Curr Eye Res 31 : 557 562.
123. Yockman JW, Kim WJ, Chang CW, Kim SW (2007). Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma. Gene Ther 14 : 1399 1405.
124. Yu AE, Hewitt RE, Connor EW, Stetler-Stevenson WG (1997). Matrix metalloproteinases. Novel targets for directed cancer therapy. Drugs Aging 11 : 229 244.
125. Zeng Y, Huebener N, Fest S et al (2007). Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. Cancer Res 67 : 2331 2338.
126. Zhu Y, Tibensky I, Schmidt J et al (2008). Interferon-alpha in combination with chemotherapy has potent antiangiogenic properties in an orthotopic mouse model for pancreatic adenocarcinoma. J Immunother 31 : 28 33.
127. Zitvogel L, Tesniere A, Kroemer G (2006). Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6 : 715 727.