Wicki Andreas, Lehembre François, Wick Nikolaus, Hantusch Brigitte, Kerjaschki Dontscho, Christofori Gerhard
Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, 4058 Basel, Switzerland.
Cancer Cell. 2006 Apr;9(4):261-72. doi: 10.1016/j.ccr.2006.03.010.
The expression of podoplanin, a small mucin-like protein, is upregulated in the invasive front of a number of human carcinomas. We have investigated podoplanin function in cultured human breast cancer cells, in a mouse model of pancreatic beta cell carcinogenesis, and in human cancer biopsies. Our results indicate that podoplanin promotes tumor cell invasion in vitro and in vivo. Notably, the expression and subcellular localization of epithelial markers are unaltered, and mesenchymal markers are not induced in invasive podoplanin-expressing tumor cells. Rather, podoplanin induces collective cell migration by filopodia formation via the downregulation of the activities of small Rho family GTPases. In conclusion, podoplanin induces an alternative pathway of tumor cell invasion in the absence of epithelial-mesenchymal transition (EMT).
血小板反应蛋白1（podoplanin）是一种小的黏蛋白样蛋白，在多种人类癌症的侵袭前沿表达上调。我们研究了血小板反应蛋白1在培养的人乳腺癌细胞、胰腺β细胞癌发生的小鼠模型以及人类癌症活检组织中的功能。我们的结果表明，血小板反应蛋白1在体外和体内均促进肿瘤细胞侵袭。值得注意的是，上皮标志物的表达和亚细胞定位未改变，且在表达血小板反应蛋白1的侵袭性肿瘤细胞中未诱导间充质标志物。相反，血小板反应蛋白1通过小Rho家族GTP酶活性的下调，通过丝状伪足形成诱导集体细胞迁移。总之，在不存在上皮-间质转化（EMT）的情况下，血小板反应蛋白1诱导肿瘤细胞侵袭的另一种途径。
