Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion
Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion
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DOI：
10.1101/gad.13.1.35
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发表时间：
1999-01-01
影响因子：
10.5
通讯作者：
Stamenkovic, I
中科院分区：
文献类型：
--
作者：
Yu, Q;Stamenkovic, I
细胞表面透明质酸受体CD44促进肿瘤生长和转移的机制仍然知之甚少。在这里，我们发现CD44与小鼠乳腺癌和人黑色素瘤细胞表面的基质金属蛋白酶-9(MMP9)的一种蛋白水解型相关。CD44相关细胞表面基质金属蛋白酶-9在体外促进细胞介导的IV型胶原降解，并介导肿瘤细胞对G8成肌细胞单层的侵袭。几种不同的CD44亚型与基质金属蛋白酶-9共沉淀，CD44/基质金属蛋白酶-9共聚集被观察到依赖于CD44形成透明质酸诱导的聚集体的能力。在体内，通过可溶或截短的细胞表面CD44的过表达来破坏CD44/MMP-9簇的形成，被证明可以抑制肿瘤的侵袭性。我们的观察表明，CD44可以将基质金属蛋白酶-9锚定在细胞表面，并确定CD44介导的肿瘤侵袭机制。
The cell surface hyaluronan receptor CD44 promotes tumor growth and metastasis by mechanisms that remain poorly understood. We show here that CD44 associates with a proteolytic form of the matrix metalloproteinase-9 (MMP-9) on the surface of mouse mammary carcinoma and human melanoma cells. CD44-associated cell surface MMP-9 promotes cell-mediated collagen IV degradation in vitro and mediates tumor cell invasion of G8 myoblast monolayers. Several distinct CD44 isoforms coprecipitate with MMP-9 and CD44/MMP-9 coclustering is observed to be dependent on the ability of CD44 to form hyaluronan-induced aggregates. Disruption of CD44/MMP-9 cluster formation, by overexpression of soluble or truncated cell surface CD44, is shown to inhibit tumor invasiveness in vivo. Our observations indicate that CD44 serves to anchor MMP-9 on the cell surface and define a mechanism for CD44-mediated tumor invasion.