Tuck A B, Elliott B E, Hota C, Tremblay E, Chambers A F
Department of Pathology, University of Western Ontario, London, Canada.
J Cell Biochem. 2000 Jun 6;78(3):465-75. doi: 10.1002/1097-4644(20000901)78:3<465::aid-jcb11>3.0.co;2-c.
Osteopontin (OPN) is a secreted glycophosphoprotein which induces migration of mammary carcinoma cells, and has been implicated in the malignancy of breast carcinoma. Hepatocyte growth factor (HGF) induces cell migration of several mammary epithelial cell (MEC) lines, via activation of its cognate receptor (Met). This study examines the mechanism of OPN-induced MEC migration, in terms of the cell surface integrins involved and induction of the HGF/Met pathway. Three different MEC cell lines were used, representing different stages of tumor progression: 21PT, non-tumorigenic; 21NT, tumorigenic; non-metastatic; and MDA-MB-435, tumorigenic, highly metastatic. Human recombinant OPN was found to induce the migration of all three lines. OPN-induced migration of 21PT and 21NT cells was alphavbeta5 and beta1-integrin dependent, and alphavbeta3-independent, while that of MDA-MB-435 cells was alphavbeta3-dependent. HGF also induced migration of all three cell lines, and a synergistic response was seen to HGF and OPN together. The increased migration response to OPN was found to be associated with an initial increase in Met kinase activity (within 30 min), followed by an increase in Met mRNA and protein expression. OPN-induced cell migration is thus mediated by different cell surface integrins in MEC lines representing different stages of progression, and involves activation of the HGF receptor, Met.
骨桥蛋白（OPN）是一种分泌型糖磷蛋白，可诱导乳腺癌细胞迁移，并与乳腺癌的恶性程度有关。肝细胞生长因子（HGF）通过激活其同源受体（Met）诱导几种乳腺上皮细胞（MEC）系的细胞迁移。本研究从所涉及的细胞表面整合素和HGF/Met途径的诱导方面，探讨了OPN诱导MEC迁移的机制。使用了三种不同的MEC细胞系，代表肿瘤进展的不同阶段：21PT，非致瘤性；21NT，致瘤性、非转移性；以及MDA-MB-435，致瘤性、高转移性。发现人重组OPN可诱导所有三种细胞系的迁移。OPN诱导的21PT和21NT细胞迁移依赖于αvβ5和β1整合素，不依赖于αvβ3，而MDA-MB-435细胞的迁移则依赖于αvβ3。HGF也可诱导所有三种细胞系的迁移，并且HGF和OPN共同作用时可见协同反应。发现对OPN迁移反应的增加与Met激酶活性的初始增加（30分钟内）有关，随后是Met mRNA和蛋白表达的增加。因此，OPN诱导的细胞迁移由代表不同进展阶段的MEC系中的不同细胞表面整合素介导，并涉及HGF受体Met的激活。
