抗血管生成与肿瘤微环境关系的研究进展_West China Medical Journal

Authors：

张慧 , 刘燕扬 , 王侠 ,  罗锋

Corresponding author：

罗锋, Email: happyhuimei@126.com

Keywords：

抗血管生成; 肿瘤微环境; 研究

DOI：

10.7507/1002-0179.20130460

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血管生成是肿瘤发展、转移的重要条件。以往曾认为抗血管生成可抑制肿瘤生长并减少远处转移。最近的研究表明，抗血管生成治疗不仅可产生耐药，短期应用反而会增加肿瘤转移复发的风险，这与肿瘤微环境的反应性变化密不可分。现就抗血管生成治疗后肿瘤微环境反应性改变的研究进展作一阐述，以期对抗血管生成治疗产生耐药及增加肿瘤转移和复发风险的机制进行更深入的探讨与研究，寻找抗肿瘤治疗的新靶点，从而改善抗肿瘤血管生成治疗的效果。

Citation： 张慧,刘燕扬,王侠,罗锋. 抗血管生成与肿瘤微环境关系的研究进展. West China Medical Journal, 2013, 28(9): 1468-1471. doi: 10.7507/1002-0179.20130460 Copy

1.	Folkman J. Tumor angiogenesis: therapeutic implications[J]. N Engl J Med, 1971, 285(21): 1182-1186.
2.	Verheul HM, Hammers H, van Erp K, et al. Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model[J]. Clin Cancer Res, 2007, 13(14): 4201-4208.
3.	Shojaei F. Anti-angiogenesis therapy in cancer: current challenges and future perspectives[J]. Cancer Lett, 2012, 320(2): 130-137.
4.	Pàez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis[J]. Cancer Cell, 2009, 15(3): 220-231.
5.	Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis[J]. Cancer Cell, 2009, 15(3): 232-239.
6.	Franco M, Man S, Chen L, et al. Targeted anti-vascular endothelial growth factor receptor-2 therapy leads to short-term and long-term impairment of vascular function and increase in tumor hypoxia[J]. Cancer Res, 2006, 66(7): 3639-3648.
7.	Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma[J]. Proc Natl Acad Sci USA, 2011, 108(9): 3749-3754.
8.	Rapisarda A, Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies[J]. Drug Resist Updat, 2009, 12(3): 74-80.
9.	Liang Y, Zheng T, Song R, et al. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma[J]. Hepatology, 2013, 57(5): 1847-1857.
10.	Brahimi-Horn MC, Chiche J, Pouyssegur J. Hypoxia and cancer[J]. J Mol Med (Berl), 2007, 85(12): 1301-1307.
11.	Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1[J]. Crit Rev Oncol Hematol, 2006, 59(1): 15-26.
12.	Krishnamachary B, Zagzag D, Nagasawa H, et al. Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B[J]. Cancer Res, 2006, 66(5): 2725-2731.
13.	Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy[J]. Nat Rev Cancer, 2008, 8(8): 592-603.
14.	Crawford Y, Kasman I, Yu L, et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment[J]. Cancer Cell, 2009, 15(1): 21-34.
15.	Sennino B, Kuhnert F, Tabruyn SP, et al. Cellular source and amount of vascular endothelial growth factor and platelet-derived growth factor in tumors determine response to angiogenesis inhibitors[J]. Cancer Res, 2009, 69(10): 4527-4536.
16.	Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis[J]. Clin Cancer Res, 2011, 17(19): 6130-6139.
17.	Poschke I, Kiessling R. On the armament and appearances of human myeloid-derived suppressor cells[J]. Clin Immunol, 2012, 144(3): 250-268.
18.	Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells[J]. Nat Biotechnol, 2007, 25(8): 911-920.
19.	Finke J, Ko J, Rini B, et al. MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy[J]. Int Immunopharmacol, 2011, 11(7): 856-861.
20.	Winkler F, Kozin SV, Tong RT, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases[J]. Cancer Cell, 2004, 6(6): 553-563.
21.	Inai T, Mancuso M, Hashizume H, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts[J]. Am J Pathol, 2004, 165(1): 35-52.
22.	Lu C, Thaker PH, Lin YG, et al. Impact of vessel maturation on antiangiogenic therapy in ovarian cancer[J]. Am J Obstet Gynecol, 2008, 198(4): 477.e1-477.e10.
23.	Maniotis AJ, Folberg R, Hess A, et al. Vascular Channel formation by human melanoma cells in vivo and in vivo: vasculogenic mimicry[J]. Am J Pathol, 1999, 155(3): 739-752.
24.	Hendrix MJ, Seftor RE, Seftor EA, et al. Transendothelial function of human metastatic melanoma cells: role of the microenvironment in cell-fate determination[J]. Cancer Res, 2002, 62(3): 665-668.
25.	Sun B, Zhang D, Zhang S, et al. Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma[J]. Cancer Lett, 2007, 249(2): 188-197.
26.	尧良清, 丰有吉, 丁景新, 等. 缺氧诱导卵巢上皮性癌细胞形成拟态血管的前期研究[J]. 中华妇产科杂志， 2005, 40(10): 662-665.
27.	Chaffer CL, Brueckmann I, Scheel C, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state[J]. Proc Natl Acad Sci USA, 2011, 108(19): 7950-7955.
28.	Li Z, Bao S, Wu Q, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells[J]. Cancer Cell, 2009, 15(6): 501-513.
29.	Krishnamachary B, Penet MF, Nimmagadda S, et al. Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer[J]. PLoS One, 2012, 7(8): e44078.
30.	Amaravadi RK, Thompson CB. The roles of therapy-induced autophagy and necrosis in cancer treatment[J]. Clin Cancer Res, 2007, 13(24): 7271-7279.
31.	Hu YL, Delay M, Jahangiri A, et al. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma[J]. Cancer Res, 2012, 72(7): 1773-1783.

1. 　Folkman J. Tumor angiogenesis: therapeutic implications[J]. N Engl J Med, 1971, 285(21): 1182-1186.
2. 　Verheul HM, Hammers H, van Erp K, et al. Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model[J]. Clin Cancer Res, 2007, 13(14): 4201-4208.
3. 　Shojaei F. Anti-angiogenesis therapy in cancer: current challenges and future perspectives[J]. Cancer Lett, 2012, 320(2): 130-137.
4. 　Pàez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis[J]. Cancer Cell, 2009, 15(3): 220-231.
5. 　Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis[J]. Cancer Cell, 2009, 15(3): 232-239.
6. 　Franco M, Man S, Chen L, et al. Targeted anti-vascular endothelial growth factor receptor-2 therapy leads to short-term and long-term impairment of vascular function and increase in tumor hypoxia[J]. Cancer Res, 2006, 66(7): 3639-3648.
7. 　Keunen O, Johansson M, Oudin A, et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma[J]. Proc Natl Acad Sci USA, 2011, 108(9): 3749-3754.
8. 　Rapisarda A, Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies[J]. Drug Resist Updat, 2009, 12(3): 74-80.
9. 　Liang Y, Zheng T, Song R, et al. Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel-Lindau tumor suppressor-dependent HIF-1α inhibition in hepatocellular carcinoma[J]. Hepatology, 2013, 57(5): 1847-1857.
10. 　Brahimi-Horn MC, Chiche J, Pouyssegur J. Hypoxia and cancer[J]. J Mol Med (Berl), 2007, 85(12): 1301-1307.
11. 　Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1[J]. Crit Rev Oncol Hematol, 2006, 59(1): 15-26.
12. 　Krishnamachary B, Zagzag D, Nagasawa H, et al. Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B[J]. Cancer Res, 2006, 66(5): 2725-2731.
13. 　Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy[J]. Nat Rev Cancer, 2008, 8(8): 592-603.
14. 　Crawford Y, Kasman I, Yu L, et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment[J]. Cancer Cell, 2009, 15(1): 21-34.
15. 　Sennino B, Kuhnert F, Tabruyn SP, et al. Cellular source and amount of vascular endothelial growth factor and platelet-derived growth factor in tumors determine response to angiogenesis inhibitors[J]. Cancer Res, 2009, 69(10): 4527-4536.
16. 　Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis[J]. Clin Cancer Res, 2011, 17(19): 6130-6139.
17. 　Poschke I, Kiessling R. On the armament and appearances of human myeloid-derived suppressor cells[J]. Clin Immunol, 2012, 144(3): 250-268.
18. 　Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells[J]. Nat Biotechnol, 2007, 25(8): 911-920.
19. 　Finke J, Ko J, Rini B, et al. MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy[J]. Int Immunopharmacol, 2011, 11(7): 856-861.
20. 　Winkler F, Kozin SV, Tong RT, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases[J]. Cancer Cell, 2004, 6(6): 553-563.
21. 　Inai T, Mancuso M, Hashizume H, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts[J]. Am J Pathol, 2004, 165(1): 35-52.
22. 　Lu C, Thaker PH, Lin YG, et al. Impact of vessel maturation on antiangiogenic therapy in ovarian cancer[J]. Am J Obstet Gynecol, 2008, 198(4): 477.e1-477.e10.
23. 　Maniotis AJ, Folberg R, Hess A, et al. Vascular Channel formation by human melanoma cells in vivo and in vivo: vasculogenic mimicry[J]. Am J Pathol, 1999, 155(3): 739-752.
24. 　Hendrix MJ, Seftor RE, Seftor EA, et al. Transendothelial function of human metastatic melanoma cells: role of the microenvironment in cell-fate determination[J]. Cancer Res, 2002, 62(3): 665-668.
25. 　Sun B, Zhang D, Zhang S, et al. Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma[J]. Cancer Lett, 2007, 249(2): 188-197.
26. 　尧良清, 丰有吉, 丁景新, 等. 缺氧诱导卵巢上皮性癌细胞形成拟态血管的前期研究[J]. 中华妇产科杂志， 2005, 40(10): 662-665.
27. 　Chaffer CL, Brueckmann I, Scheel C, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state[J]. Proc Natl Acad Sci USA, 2011, 108(19): 7950-7955.
28. 　Li Z, Bao S, Wu Q, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells[J]. Cancer Cell, 2009, 15(6): 501-513.
29. 　Krishnamachary B, Penet MF, Nimmagadda S, et al. Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer[J]. PLoS One, 2012, 7(8): e44078.
30. 　Amaravadi RK, Thompson CB. The roles of therapy-induced autophagy and necrosis in cancer treatment[J]. Clin Cancer Res, 2007, 13(24): 7271-7279.
31. 　Hu YL, Delay M, Jahangiri A, et al. Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma[J]. Cancer Res, 2012, 72(7): 1773-1783.

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抗血管生成与肿瘤微环境关系的研究进展

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