Onoue Tomitaro, Uchida Daisuke, Begum Nasima Mila, Tomizuka Yoshifumi, Yoshida Hideo, Sato Mitsunobu
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Int J Oncol. 2006 Nov;29(5):1133-8.
Epithelial-mesenchymal transition (EMT) refers to critical events occasionally observed during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral squamous cell carcinoma (SCC), we have explored the possibility that this system might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional CXCR4 and lymph node metastatic potential, were found to lose their epithelial cell morphology due to SDF-1. In this context, the downregulation of epithelial markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions, but the effect was impaired by treatment with Wortmannin. These results suggested that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.
上皮-间质转化（EMT）指的是在肿瘤进展过程中偶尔观察到的关键事件，包括侵袭和转移，在此过程中癌细胞获得成纤维细胞样表型。由于基质细胞衍生因子-1（SDF-1）/CXCR4系统可促进口腔鳞状细胞癌（SCC）的淋巴结转移，我们探讨了该系统可能参与上皮-间质转化的可能性。发现具有功能性CXCR4和淋巴结转移潜能的口腔SCC细胞B88和HNt因SDF-1而失去上皮细胞形态。在此情况下，检测到上皮标志物细胞角蛋白、E-钙黏蛋白和β-连环蛋白的下调，以及间充质标志物波形蛋白和蜗牛蛋白的上调。此外，磷脂酰肌醇3激酶（PI3K）抑制剂渥曼青霉素可抑制SDF-1处理导致的波形蛋白上调，但丝裂原活化蛋白激酶/细胞外信号调节激酶抑制剂U0126则无此作用。在I型胶原包埋培养中，SDF-1处理的B88细胞形成突出的延伸，但渥曼青霉素处理可削弱该作用。这些结果表明，SDF-1/CXCR4系统诱导的上皮-间质转化可能通过激活PI3K-Akt/PKB途径参与口腔SCC的淋巴结转移。
