Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.
Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.
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DOI：
10.1101/gad.14.2.163
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发表时间：
2000-01
影响因子：
10.5
通讯作者：
Q. Yu;I. Stamenkovic
中科院分区：
文献类型：
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作者：
Q. Yu;I. Stamenkovic
我们已经发现了透明质酸受体CD 44，基质金属蛋白酶-9（MMP-9）和多功能细胞因子TGF-β在控制肿瘤相关组织重塑中的新功能关系。CD 44为具有蛋白水解活性的MMP-9提供了一个细胞表面对接受体，我们在这里表明MMP-9定位于细胞表面是其促进肿瘤侵袭和血管生成的能力所必需的。我们的观察结果还表明，MMP-9，以及MMP-2，蛋白水解裂解潜伏的TGF-β，提供了一个新的和潜在的重要的TGF-β激活机制。此外，我们发现MMP-9定位于正常角质形成细胞的表面是CD 44依赖性的，并且可以激活潜伏的TGF-β。这些观察结果表明，协调的CD 44，MMP-9和TGF-β功能可能提供了组织重塑的生理机制，可以通过恶性细胞促进肿瘤生长和侵袭。
We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-beta in the control of tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote tumor invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-beta, providing a novel and potentially important mechanism for TGF-beta activation. In addition, we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-beta. These observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.