Ramchandran Ramani, Karumanchi S Ananth, Hanai Jun-ichi, Alper Seth L, Sukhatme Vikas P
Division of Nephrology, Department of Medicine and Center for Study of the Tumor Microenvironment, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Crit Rev Eukaryot Gene Expr. 2002;12(3):175-91. doi: 10.1615/critreveukaryotgeneexpr.v12.i3.20.
The malignant transformation of a normal cell into a cancer cell requires no vasculature. Growth of solid tumors, however, requires angiogenesis to provide oxygen and nutrients to support cell proliferation. The switch from an avascular to a vascular phenotype is typically associated with acceleration of tumor growth. Antiangiogenic therapy, starving a tumor of its blood supply, is an attractive addition to the anticancer armamentarium. Animal tests of antiangiogenic therapy have shown remarkable potential. Initial human trials have proven antiangiogenic therapy to be remarkably nontoxic. Numerous antiangiogenic agents have been isolated as proteolytic fragments of endogenous polypeptides of the extracellular matrix. Endostatin was the first such antiangiogenic protein described and its potent antitumor effects in mice have generated wide interest. This review summarizes recent advances in endostatin biology and highlights new results on the cellular and subcellular mechanisms of endostatin action.
正常细胞向癌细胞的恶性转化并不需要脉管系统。然而，实体瘤的生长需要血管生成来提供氧气和营养物质以支持细胞增殖。从无血管表型向血管表型的转变通常与肿瘤生长加速相关。抗血管生成疗法，即切断肿瘤的血液供应，是抗癌武器库中一个有吸引力的补充。抗血管生成疗法的动物试验已显示出显著的潜力。最初的人体试验已证明抗血管生成疗法具有显著的低毒性。许多抗血管生成剂已被分离为细胞外基质内源性多肽的蛋白水解片段。内皮抑素是首个被描述的此类抗血管生成蛋白，其在小鼠体内的强大抗肿瘤作用引起了广泛关注。本综述总结了内皮抑素生物学的最新进展，并突出了关于内皮抑素作用的细胞和亚细胞机制的新结果。
