Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5
Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5
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DOI：
10.1126/science.277.5323.225
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发表时间：
1997-07-11
期刊：
影响因子：
56.9
通讯作者：
Quaranta, V
中科院分区：
文献类型：
--
作者：
Giannelli, G;FalkMarzillier, J;Quaranta, V
细胞外基质的结构变化是组织重建和肿瘤侵袭过程中细胞迁移所必需的。层粘连蛋白-5（Ln-5）被基质金属蛋白酶-2（MMP-2）特异性切割，可诱导乳腺上皮细胞迁移。MMP 2在残基587处切割Ln-5 γ 2亚基，从而暴露出Ln-5上的一个假定的隐蔽的促迁移位点，该位点触发细胞运动。这种改变形式的Ln-5存在于肿瘤和正在重塑的组织中，但不在静止组织中。MMP 2对Ln-5的切割以及由此产生的Ln-5隐蔽位点的激活可能为调节肿瘤细胞侵袭和组织重塑提供新的靶点。
Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Specific cleavage of laminin-5 (Ln-5) by matrix metalloprotease-2 (MMP2) was shown to induce migration of breast epithelial cells. MMP2 cleaved the Ln-5 gamma 2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.