Inhibitory mechanism of vascular endothelial cell proliferation by endostatin

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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.