INCREASED PROTEOLYTIC ACTIVITY IS RESPONSIBLE FOR THE ABERRANT MORPHOGENETIC BEHAVIOR OF ENDOTHELIAL-CELLS EXPRESSING THE MIDDLE T-ONCOGENE
INCREASED PROTEOLYTIC ACTIVITY IS RESPONSIBLE FOR THE ABERRANT MORPHOGENETIC BEHAVIOR OF ENDOTHELIAL-CELLS EXPRESSING THE MIDDLE T-ONCOGENE
复制标题
蛋白水解活性的增加是表达中间 t-癌基因的内皮细胞形态发生行为异常的原因
DOI：
10.1016/0092-8674(90)90009-4
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发表时间：
1990-08-10
期刊：
影响因子：
64.5
通讯作者：
ORCI, L
中科院分区：
文献类型：
--
作者：
MONTESANO, R;PEPPER, MS;ORCI, L
多瘤病毒中T(Mt)癌基因在体内的表达与对正常血管发育的深刻颠覆有关，从而导致内皮性肿瘤(血管瘤)的形成。为了了解这一现象的分子机制，我们在体外系统中研究了表达该癌基因的内皮细胞的形态发生特性。在纤维蛋白凝胶中生长的表达MT的内皮瘤(END)细胞形成大的血管瘤样囊状结构。所有被检测的终末细胞株都表现出高水平的纤溶活性，这是由于尿激酶型纤溶酶原激活剂的产生增加和纤溶酶原激活物抑制物的产生减少所致。外源添加的丝氨酸蛋白酶抑制剂中和了过量的蛋白水解酶活性，纠正了终末细胞在体外的异常行为，并允许形成毛细血管样小管。这些结果表明，严密控制的蛋白水解酶活性对血管形态发生至关重要，生理性蛋白水解酶抑制剂在血管形成中起着重要的调节作用。
Expression of polyoma virus middle T (mT) oncogene in vivo is associated with a profound subversion of normal vascular development, which results in the formation of endothelial tumors (hemangiomas). In an attempt to understand the molecular mechanisms responsible for this phenomenon, we have investigated, in an in vitro system, the morphogenetic properties of endothelial cells expressing this oncogene. mT-expressing endothelioma (End) cells grown within fibrin gels formed large hemangioma-like cystic structures. All End cell lines examined expressed high levels of fibrinolytic activity resulting from increased production of urokinase-type plasminogen activator and decreased production of plasminogen activator inhibitors. Neutralization of excess proteolytic activity by exogenously added serine protease inhibitor corrected the aberrant in vitro behavior of End cells and allowed the formation of capillary-like tubules. These results suggest that tightly controlled proteolytic activity is essential for vascular morphogenesis and that physiological protease inhibitors play an important regulatory role in angiogenesis.