Liotta L A, Wewer U, Rao N C, Schiffmann E, Stracke M, Guirguis R, Thorgeirsson U, Muschel R, Sobel M
Laboratory of Pathology, NCI, Bethesda, MD 20892.
Prog Clin Biol Res. 1988;256:3-16.
Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.
癌症侵袭和转移是一个复杂的多步骤过程。为了使肿瘤细胞成功跨越这个过程的所有步骤并启动转移灶，它必须表达正确组合的基因产物。这类基因产物可能包括调节细胞与基底膜相互作用以及细胞运动性的蛋白质。肿瘤细胞通过细胞表面的层粘连蛋白受体附着于基底膜糖蛋白层粘连蛋白。人层粘连蛋白受体已被纯化并进行了分子克隆。多种人类癌细胞中层粘连蛋白受体mRNA的水平与这些细胞表面层粘连蛋白受体的数量相关。附着于基底膜后，肿瘤细胞接着分泌可能降解IV型胶原的蛋白酶。利用我们新的采用ras癌基因诱导转移的遗传系统，研究了IV型胶原酶分泌与转移之间的遗传联系。在附着和局部蛋白水解之后，侵袭的第三步是肿瘤细胞运动。我们已经分离出一种肿瘤细胞自分泌运动因子（AMF）。该因子由肿瘤细胞分泌并与细胞表面受体结合，从而导致细胞运动受到显著（超过100倍）刺激。AMF可能在肿瘤细胞的自主侵袭行为中起主要作用。
