Interaction of endostatin with integrins implicated in angiogenesis

Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with α(5)- and α(v)-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin–integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.

内皮抑素（Endostatin）是XVIII型胶原（collagen XVIII）的一段肽段，为强效血管生成拮抗剂，在小鼠模型中可抑制肿瘤生长。目前，内皮抑素的作用机制尚不明确。本研究证实，重组表达的人源内皮抑素可与人内皮细胞表面的α(5)整合素与α(v)整合素相结合。进一步研究表明，内皮抑素与整合素（integrins）的相互作用具备体外功能意义：我们发现固定化的内皮抑素可通过整合素依赖的方式促进内皮细胞存活与迁移；而可溶性内皮抑素则会抑制整合素依赖的内皮细胞功能，如细胞迁移。综上，上述结果提示整合素可作为内皮抑素发挥功能的潜在靶点，同时佐证了整合素在内皮细胞生物学及血管生成过程中的重要作用。