The 72 kDa type IV collagenase is modulated via differential expression of alpha v beta 3 and alpha 5 beta 1 integrins during human melanoma cell invasion.
The 72 kDa type IV collagenase is modulated via differential expression of alpha v beta 3 and alpha 5 beta 1 integrins during human melanoma cell invasion.
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发表时间：
1993-07
期刊：
影响因子：
11.2
通讯作者：
R. E. Seftor;E. Seftor;W. Stetler-Stevenson;M. Hendrix
中科院分区：
文献类型：
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作者：
R. E. Seftor;E. Seftor;W. Stetler-Stevenson;M. Hendrix
我们最近报道，伴随着侵袭性的增加，在中等侵袭性的人黑色素瘤细胞系（A375 M）中，在α v β 3经典玻连蛋白受体扰动后，基质降解72 kDa明胶酶A/IV型胶原酶（MMP-2）的表达和分泌增加。在本研究中，我们将这些观察结果扩展到包括高度侵袭性和转移性黑素瘤细胞系（C8161），其表达相当数量的α 5 β 1整联蛋白（经典纤连蛋白受体），但其表面上的α v β 3整联蛋白非常少。当用抗α 5 β 1抗体干扰时，C8161细胞在体外的侵袭性增加89%，并且表达和分泌增加水平的明胶酶A。使用α v β 3整联蛋白的抗体不能引起这些变化。此外，C8161细胞通过纤连蛋白增强的基质的侵袭增加了73%，这可以被明胶酶A的中和抗体消除。此外，我们试图通过荧光激活细胞分选选择或脱氧野尻霉素处理减少A375 M细胞表面的α v β 3整联蛋白来瞬时模拟C8161细胞的侵袭性表型，并发现这些细胞的侵袭性比亲本群体高30-50%。这些数据表明，作为整合素差异表达的结果，可能参与黑色素瘤肿瘤细胞侵袭的替代调制和信号传导事件，并且严格编目这些整合素的存在只是分析其功能活性的初始步骤。
We have recently reported that concomitant with an increase in invasiveness, there is an increase in the expression and secretion of the matrix-degrading 72 kDa gelatinase A/type IV collagenase (MMP-2) in a moderately invasive human melanoma cell line (A375M) upon perturbation of the alpha v beta 3 classic vitronectin receptor. In the present study, we have extended these observations to include a highly invasive and metastatic melanoma cell line (C8161) which expresses a comparable amount of the alpha 5 beta 1 integrin (classic fibronectin receptor), but very little alpha v beta 3 integrin on its surface. When perturbed with an anti-alpha 5 beta 1 antibody, C8161 cells are 89% more invasive in vitro, and express and secrete increased levels of the gelatinase A. These changes were not elicited using antibodies to the alpha v beta 3 integrin. In addition, a 73% increase in invasion of C8161 cells through a fibronectin-enhanced matrix occurred, which could be abrogated by neutralizing antibodies to gelatinase A. Furthermore, we attempted to transiently mimic the invasive phenotype of the C8161 cells by diminishing the alpha v beta 3 integrin from the A375M cell surface through fluorescence-activated cell sorting selection or deoxynojirimycin treatment, and found these cells to be 30-50% more invasive than the parental population. These data suggest that alternative modulation and signaling events could be involved in melanoma tumor cell invasion as a result of the differential expression of integrins, and strictly cataloging the presence of these integrins is but an initial step in the analysis of their functional activity.