Biochemical mechanisms of tumor invasion and metastasis.
Biochemical mechanisms of tumor invasion and metastasis.
复制标题
肿瘤侵袭和转移的生化机制。
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
M. Sobel
中科院分区：
文献类型：
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作者：
L. Liotta;U. Wewer;N. C. Rao;E. Schiffmann;M. Stracke;R. Guirguis;U. Thorgeirsson;R. Muschel;M. Sobel
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地完成该过程的所有步骤并启动转移集落，它必须表达正确的基因产物组合。此类基因产物可包括调节细胞与基底膜相互作用和细胞运动的蛋白质。肿瘤细胞通过细胞表面层粘连蛋白受体附着在基底膜糖蛋白层粘连蛋白上。纯化并分子克隆人层粘连蛋白受体。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。附着在基底膜上后，肿瘤细胞接下来会分泌可能降解 IV 型胶原蛋白的蛋白酶。 IV 型胶原酶分泌与转移之间的遗传联系是胶原蛋白。使用我们的新遗传系统研究了 IV 型胶原酶分泌与转移之间的遗传联系，该系统通过 ras 癌基因诱导转移。附着和局部蛋白水解之后，侵袭的第三步是肿瘤细胞运动。我们分离出了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，从而对细胞运动产生深度（大于 100 倍）刺激。 AMF可能在肿瘤细胞的自主侵袭行为中发挥重要作用。
Cancer invasion and metastases is a complex multi-step 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 in a variety of human carcinoma cells correlated with the number of laminin receptors on the 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 collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases by 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 100 x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.