Tumor angiogenesis.
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.
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Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129, USA. michael.detmar@cbrc2.mgh.harvard.edu
D000818:Animals; D016228:Endothelial Growth Factors / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D019700:Thrombospondin 1 / Q000502:physiology; D019699:Thrombospondins / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019700:Thrombospondin 1; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2