A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer.
A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer.
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发表时间：
1997-04
期刊：
影响因子：
11.2
通讯作者：
B. K. Sim;Michael S. O'Reilly;Hong Liang;A. Fortier;Weixuan He;John W. Madsen;Randall K. Lapcevich;Carol A. Nacy
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作者：
B. K. Sim;Michael S. O'Reilly;Hong Liang;A. Fortier;Weixuan He;John W. Madsen;Randall K. Lapcevich;Carol A. Nacy
内源性鼠血管抑素，被鉴定为纤溶酶原的内部片段，在体内阻断实验性原发性和转移性肿瘤的新血管形成和生长。在巴斯德毕赤酵母中表达的包含人纤溶酶原的kringle 1 - 4（氨基酸93 - 470）的重组蛋白具有模拟天然血管抑制素的物理性质（分子大小、与赖氨酸的结合、与kringle 1 - 3的抗体的反应性）。重组Angiostatin蛋白在体外可抑制牛毛细血管内皮细胞的增殖。以1.5 mg/kg的剂量全身给予重组血管抑素蛋白，抑制C57 BL/6小鼠中刘易斯肺癌-低转移表型转移瘤的生长超过90%;以100 mg/kg的剂量给予重组蛋白还抑制原发性刘易斯肺癌-低转移表型肿瘤的生长。这些发现明确地表明内源性血管抑素的抗血管生成和抗肿瘤活性存在于纤溶酶原的kringles 1 - 4内。
Endogenous murine angiostatin, identified as an internal fragment of plasminogen, blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. A recombinant protein comprising kringles 1-4 of human plasminogen (amino acids 93-470) expressed in Pichia pastoris had physical properties (molecular size, binding to lysine, reactivity with antibody to kringles 1-3) that mimicked native angiostatin. This recombinant Angiostatin protein inhibited the proliferation of bovine capillary endothelial cells in vitro. Systemic administration of recombinant Angiostatin protein at doses of 1.5 mg/kg suppressed the growth of Lewis lung carcinoma-low metastatic phenotype metastases in C57BL/6 mice by greater than 90%; administration of the recombinant protein at doses of 100 mg/kg also suppressed the growth of primary Lewis lung carcinoma-low metastatic phenotype tumors. These findings demonstrate unambiguously that the antiangiogenic and antitumor activity of endogenous angiostatin resides within kringles 1-4 of plasminogen.