Inhibitory mechanism of vascular endothelial cell proliferation by endostatin

在低氧条件下，培养的血管内皮细胞XVIII基因的表达明显降低。特异性单克隆抗体分析时，胶原XVIII蛋白水平也降低。内皮抑素在体内诱导软骨肉瘤生长消退和肿瘤血管生成。然而，内皮抑素对软骨肉瘤细胞的体外增殖和迁移没有影响。接下来，我们详细研究了内皮抑素和内皮细胞之间的相互作用。内皮抑素抑制I型胶原的迁移和附着，但不影响内皮细胞的增殖。虽然血管生成因子如碱性成纤维细胞生长因子和血管内皮生长因子可以刺激内皮细胞的迁移，但内皮抑素在存在或不存在兴奋剂的情况下对内皮细胞的迁移具有相似的抑制作用。我们得出结论，非血管性脑转移主要包含两种类型中的一种；即，上皮下基底膜一般含有XVIII型，而骨骼肌和心肌则主要含有XV型。但是血管组织中平滑肌细胞周围的基底膜根据它们的位置，包含其中一种或两种。有趣的是，连续或体细胞毛细血管的基底膜中同时含有XV型和XVIII型胶原；然而，开孔毛细血管或特化毛细血管，如肾小球、肝窦、肺泡和脾窦，其基底膜仅表达XVIII型链，缺乏XV型链。这一观察结果可能暗示不同组织和器官中基底膜的不同功能使用不同的内源性血管生成控制机制。

Under low oxygen condition, expression of collagen XVIII gene by cultured vascular endothelial cells reduced significantly. When it was analyzed by specific monoclonal antibodies, the collagen XVIII protein level was also reduced.Endostatin induced regression of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effects on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration and attachment on collagen I but did not affect proliferation of endothelial cells. Although the migration of endothelial cells was stimulated with angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence or absence of stimulants.We came to the conclusion that non-vascular BMs contain predominantly one of the two types; I.e., subepithelial basement membranes contained type XVIII in general, whereas skeletal and cardiac muscles harbored prominently type XV. But basement membranes surrounding smooth muscle cells in vascular tissues contained one or both of them, depending on their locations. Interestingly, continuous or somatic capillaries contained both type XV and type XVIII collagens in their basement membranes; however, fenestrated or specialized capillaries such as glomeruli, liver sinusoids, lung alveoli, and splenic sinusoids expressed only type XVIII chains in their basement membranes, lacking type XV chain. This observation could imply different functions of basement membranes in various tissues and organs that use different mechanisms for the endogenous control of angiogenesis.