内皮细胞生长抑制素——抗肿瘤血管生成的细胞因子

内皮细胞生长抑制素——抗肿瘤血管生成的细胞因子 Endostatin:a Cell Factor of Antiangogenesis in Tumor Groth and Metastase 吕碧文 LU Bi\|wen 1 first-author 胡敏 HU Min 1 齐义鹏 QI Yi\|peng 1 武汉大学病毒研究所,湖北,武汉,430072 武汉大学病毒研究所,湖北,武汉,430072 Institute of Viology,Collage of Life Sciences,Wuhan University Institute of Viology,Collage of Life Sciences,Wuhan University 综述了内皮细胞生长抑制素的结构和功能 ;探讨了其与胶原蛋白 的关系以及抗血管生成、抗肿瘤生长和转移的可能机理 ;展望了其在肿瘤诊断、治疗等方面的应用前景 .内皮细胞生长抑制素是胶原蛋白 C-末端的酶解产物 ,在血管生成过程中起负调控作用 ,通过阻断血管生成的信号并诱导内皮细胞的凋亡而特异性地抑制内皮细胞的迁移和新血管的生成 ,从而抑制肿瘤的生长和转移 .其抗血管生成的机制目前尚未完全清楚 ,研究显示它是一个结合紧密的球状折叠分子 ,一面富含精氨酸残基 ,是肝素的结合位点 ,推测与抗血管生成的机制有关 .内皮细胞生长抑制素作为抗肿瘤的内源性药物 ,具有高效性 ,低毒性 ,无耐药性等优点 endostatin is a 20×10 3 C-terminal fragment of collagenⅩⅧ,which was found in vessel walls and basement membranes.The generation of endostatin from collagenⅩⅧ is catalyzed by proteolytic enzymes,including cathepsin L and matrix metalloproteases,that cleave peptide bonds within the protease-sensitive hinge region of the c-terminal domain.The processing of collagenⅩⅧ to endostatin may represent a local control mechanism for the regulation of angiogenesis.Endostatin specially inhibits endosthelial prolifeation and potently inhibits angiogenesis and tumor groth. Endostatin can induce endothelial cellapoptosis.The molecular mechanism behind the ihibition of angiogenesis have not yet been elucideted.Studies have shown that endostatin is a compact globular fold with one face particularly rich in argine residues acting as a haparin-binding epipote.It was initially suggested that zinc has a structural rather than a functional role in endostatin .As an endosgenous drugs of angiogenesis and tumor groth,endostatin has shown many advantages:highly effeciacy,lowest toxivity and no drug resistance. 内皮细胞生长抑制素 胶原蛋白ⅩⅧ 抗肿瘤血管生成 细胞因子 endostatin collagenⅩⅧ antiangiogenesis cell factor Q512.5 2001-02-01 2021-04-01 2