Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1
Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1
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DOI：
10.1073/pnas.170290997
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发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
DeClerck, YA
中科院分区：
文献类型：
--
作者：
Henriet, P;Zhong, ZD;DeClerck, YA
已知细胞外基质调节正常细胞增殖，并且假定不依赖于贴壁的恶性细胞逃避这种调节功能。在这里，我们证明了人M24 met黑色素瘤细胞仍然对与I型胶原接触产生的生长调节信号有反应，并且对增殖的影响取决于胶原的物理结构。在聚合的纤维状胶原上，M24 met细胞在G（1）/S检查点生长停滞，并维持高水平的p27（KIP 1）mRNA和蛋白。相反，在非纤维（变性）胶原蛋白上，细胞进入细胞周期，p27（KIP 1）下调。这些生长调节作用涉及I型胶原和胶原结合整合素α（2）β（1）之间的接触，其在纤维状胶原存在下似乎受到限制。因此，黑色素瘤细胞对源自纤维胶原的负生长调节信号保持敏感，并且纤维的蛋白水解降解是允许肿瘤细胞逃避这些限制性信号的机制。
It is known that the extracellular matrix regulates normal cell proliferation, and it is assumed that anchorage-independent malignant cells escape this regulatory function. Here we demonstrate that human M24met melanoma cells remain responsive to growth regulatory signals that result from contact with type I collagen and that the effect on proliferation depends on the physical structure of the collagen. On polymerized fibrillar collagen, M24met cells are growth arrested at the G(1)/S checkpoint and maintain high levels of p27(KIP1) mRNA and protein. In contrast, on nonfibrillar (denatured) collagen, the cells enter the cell cycle, and p27(KIP1) is downregulated. These growth regulatory effects involve contact between type I collagen and the collagen-binding integrin alpha(2)beta(1) which appears restricted in the presence of fibrillar collagen. Thus melanoma cells remain sensitive to negative growth regulatory signals originating from fibrillar collagen, and the proteolytic degradation of fibrils is a mechanism allowing tumor cells to escape these restrictive signals.