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肿瘤的生长和转移离不开新生血管的形成。Hexastatin是一种新型的肿瘤血管生成抑制剂,它来源于细胞外基质,是Ⅳ型胶原蛋白α6链的非胶原区NC1,相对分子质量为25000。Hexastatin的分布具有明显的组织特异性。Hexastatin可以通过一种RGD非依赖方式与整合素分子αvβ3结合,调节内皮细胞的黏附和迁移,并且剂量依赖性地抑制内皮细胞的增殖,对抑制血管生成起到显著的作用。Hexastatin能抑制80%～90%的经bFGF刺激的鸡胚绒毛膜血管的生成,抑制90%的人脐静脉内皮细胞的迁移,Hexastatin还能有力地(大约60%)抑制CS1黑素瘤细胞的生长。在已建立的肿瘤小鼠模型中,Hexasta-tin能抑制小鼠肺癌移植瘤生长。在癌细胞浸润过程中,α6(Ⅳ)链经常会在癌细胞巢穴周围的基底膜区域中缺失,使得Hex-astatin在癌组织中含量下调,从而成为诊断肿瘤浸润的重要指标。Hexastatin作为新型的肿瘤血管生成抑制剂在肿瘤的防治中具有重要的研究和应用前景。
Tumor growth and metastasis can not be separated from the formation of new blood vessels. Hexastatin is a novel tumor angiogenesis inhibitor derived from the extracellular matrix. It is a non-collagenous NC1 of the α6 chain of type Ⅳ collagen with a relative molecular mass of 25,000. Hexastatin distribution has obvious tissue specificity. Hexastatin can regulate the adhesion and migration of endothelial cells by binding to the integrin αvβ3 in an RGD-independent manner and plays a significant role in inhibiting angiogenesis by inhibiting the proliferation of endothelial cells in a dose-dependent manner. Hexastatin inhibits 80% to 90% of bFGF-stimulated chick embryo chorionic vasculature, inhibits 90% of human umbilical vein endothelial cell migration, and Hexastatin also potently (about 60%) inhibits CS1 melanoma cells Grow. In established tumor mouse model, Hexasta-tin can inhibit the growth of mouse lung cancer xenografts. During the infiltration of cancer cells, the α6 (Ⅳ) chain is often absent in the basement membrane region around the cancer cell nests, making the content of Hex-astatin decreased in cancer tissues, which becomes an important indicator of tumor invasion. As a new tumor angiogenesis inhibitor, Hexastatin has important research and application prospects in the prevention and treatment of tumors.