抗血管生成與腫瘤微環境關系的研究進展_《華西醫學》

作者：

張慧 , 劉燕揚 , 王俠 ,  羅鋒

四川大學華西醫院腫瘤科（成都，610041）;

關鍵詞：

抗血管生成腫瘤微環境研究

DOI：

10.7507/1002-0179.20130460

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

血管生成是腫瘤發展、轉移的重要條件。以往曾認為抗血管生成可抑制腫瘤生長并減少遠處轉移。最近的研究表明，抗血管生成治療不僅可產生耐藥，短期應用反而會增加腫瘤轉移復發的風險，這與腫瘤微環境的反應性變化密不可分。現就抗血管生成治療后腫瘤微環境反應性改變的研究進展作一闡述，以期對抗血管生成治療產生耐藥及增加腫瘤轉移和復發風險的機制進行更深入的探討與研究，尋找抗腫瘤治療的新靶點，從而改善抗腫瘤血管生成治療的效果。

引用本文： 張慧,劉燕揚,王俠,羅鋒. 抗血管生成與腫瘤微環境關系的研究進展. 華西醫學, 2013, 28(9): 1468-1471. doi: 10.7507/1002-0179.20130460 復制

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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.
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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.	堯良清, 豐有吉, 丁景新, 等. 缺氧誘導卵巢上皮性癌細胞形成擬態血管的前期研究[J]. 中華婦產科雜志， 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. 　堯良清, 豐有吉, 丁景新, 等. 缺氧誘導卵巢上皮性癌細胞形成擬態血管的前期研究[J]. 中華婦產科雜志， 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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抗血管生成與腫瘤微環境關系的研究進展

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