Detmar M
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129, USA.
J Investig Dermatol Symp Proc. 2000 Dec;5(1):20-3. doi: 10.1046/j.1087-0024.2000.00003.x.
In order to grow beyond minimal size and to metastasize, tumors need to induce the growth of new blood vessels (angiogenesis). Whereas in normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli, tumor angiogenesis is induced by increased secretion of angiogenic factors and/or by downregulation of angiogenesis inhibitors. Recent evidence suggests vascular endothelial growth factor (VEGF) as the major tumor angiogenesis factor, promoting tumor growth, invasion, and metastasis. Conversely, blocking of VEGF function inhibits angiogenesis and suppresses tumor growth in vivo. Newly identified members of the VEGF family of angiogenesis factors include placental growth factor, VEGF-B, VEGF-C, and VEGF-D, and show overlapping binding patterns to specific endothelial cell receptors. VEGF-C appears to play a major role as a lymphangiogenesis factor and as a growth factor for Kaposi's sarcoma. In contrast, endogenous inhibitors prevent blood vessel growth in normal tissues. In particular, thrombospondin-1 (TSP-1) and TSP-2 are expressed in normal skin and, when introduced into squamous cell carcinomas, potently inhibit malignant tumor growth via inhibition of tumor angiogenesis.
为了生长到超过最小尺寸并发生转移，肿瘤需要诱导新血管生成（血管生成）。在正常组织中，内源性血管生成抑制剂对血管生成刺激的主导作用维持着血管静止状态，而肿瘤血管生成则是由血管生成因子分泌增加和/或血管生成抑制剂下调所诱导。最近的证据表明血管内皮生长因子（VEGF）是主要的肿瘤血管生成因子，促进肿瘤生长、侵袭和转移。相反，阻断VEGF功能可抑制血管生成并在体内抑制肿瘤生长。新发现的血管生成因子VEGF家族成员包括胎盘生长因子、VEGF-B、VEGF-C和VEGF-D，它们与特定内皮细胞受体的结合模式重叠。VEGF-C似乎作为淋巴管生成因子和卡波西肉瘤的生长因子发挥主要作用。相比之下，内源性抑制剂可阻止正常组织中的血管生长。特别是，血小板反应蛋白-1（TSP-1）和TSP-2在正常皮肤中表达，当引入鳞状细胞癌时，可通过抑制肿瘤血管生成有效抑制恶性肿瘤生长。
