Matrix metalloproteinase-2 activation modulates glioma cell migration.
Matrix metalloproteinase-2 activation modulates glioma cell migration.
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发表时间：
1997-10
影响因子：
4
通讯作者：
E. Deryugina;M. Bourdon;Guang-Xiang Luo;Ralph A. Reisfeld;A. Strongin
中科院分区：
文献类型：
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作者：
E. Deryugina;M. Bourdon;Guang-Xiang Luo;Ralph A. Reisfeld;A. Strongin
用编码MT-MMP-1的cDNA稳定转染U251.3胶质瘤细胞，导致MT-MMP-1和TIMP-2细胞表面表达增加，MMP-2前酶组成性激活，胶原降解增加。在肿瘤球体生长试验中，MT-MMP-1转染物相对于对照的细胞迁移在胶原蛋白上增强，在玻璃体连接蛋白和纤维连接蛋白上减弱。这些作用被TIMP-2逆转，并且与细胞粘附的任何实质性变化无关。抗（α）vss3整合素阻断抗体特异性抑制了U251.3细胞与MMP-2 c -末端结构域的结合，表明MMP-2通过酶的c -末端部分在整合素基质粘附位点或附近与（α）vss3相互作用。我们提出这些机制可以通过在细胞表面隔离活性MMP-2来控制肿瘤细胞微环境中基质的定向降解。我们的数据表明，MMP-2的激活及其在细胞表面的蛋白水解活性可以通过改变细胞外基质的组成和细胞表面粘附受体的表达来不同地调节肿瘤细胞对特定基质蛋白的迁移。
Stable transfection of U251.3 glioma cells with cDNA encoding MT-MMP-1 resulted in increased cell surface expression of MT-MMP-1 and TIMP-2, constitutive activation of MMP-2 proenzyme and increased collagen degradation. In tumor spheroid outgrowth assays, cell migration of MT-MMP-1 transfectants relative to control was enhanced on collagen and decreased on vitronectin and fibronectin. These effects were reversed by TIMP-2 and were not associated with any substantial changes in cell adhesion. Binding of U251.3 cells to the C-terminal domain of MMP-2 was specifically inhibited by anti-(alpha)vss3 integrin blocking antibody indicating that MMP-2 interacts with (alpha)vss3 through the enzyme's C-terminal portion at or near the integrin's matrix adhesion sites. We propose that these mechanisms could govern directed matrix degradation in the tumor cells' microenvironment by sequestration of active MMP-2 on the cell surface. Our data suggest that activation of MMP-2 and its proteolytic activity localized to the cell surface could differentially modulate tumor cell migration in response to particular matrix proteins by altering both composition of the extracellular matrix and expression of adhesion receptors on the cell surface.