Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3
Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3
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DOI：
10.1016/s0092-8674(00)81235-0
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发表时间：
1996-05-31
期刊：
影响因子：
64.5
通讯作者：
Cheresh, DA
中科院分区：
文献类型：
--
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
细胞侵袭依赖于黏附机制和蛋白水解机制之间的协同作用。有证据表明，基质金属蛋白酶MMP - 2能够以具有蛋白水解活性的形式定位于侵袭性细胞表面，这是基于它能直接结合整合素αvβ3。在体内，MMP - 2和αvβ3特异性地共定位于血管生成的血管和黑色素瘤细胞上。在培养的黑色素瘤细胞上表达αvβ3使其能够以具有蛋白水解活性的形式与MMP - 2结合，促进细胞介导的胶原蛋白降解。在体外，这些蛋白质形成一种SDS稳定的复合物，该复合物依赖于MMP - 2的非催化性C末端，因为一种截短突变体失去了结合αvβ3的能力。这些发现确定了一种单一的细胞表面受体，它既能调节基质降解又能调节细胞运动，从而促进定向的细胞侵袭。
Cellular invasion depends on cooperation between adhesive and proteolytic mechanisms. Evidence is provided that the matrix metalloproteinase MMP-2 can be localized in a proteolytically active form on the surface of invasive cells, based on its ability to bind directly integrin alpha v beta 3. MMP-2 and alpha v beta 3 were specifically colocalized on angiogenic blood vessels and melanoma cells in vivo. Expression of alpha v beta 3 on cultured melanoma cells enabled their binding to MMP-2 in a proteolytically active form, facilitating cell-mediated collagen degradation. In vitro, these proteins formed an SDS-stable complex that depended on the noncatalytic C-terminus of MMP-2, since a truncation mutant lost the ability to bind alpha v beta 3. These findings define a single cell-surface receptor that regulates both matrix degradation and motility, thereby facilitating directed cellular invasion.