Abstract 412: Isolation and analysis of metastasis-related genes in an oral cancer cells with autocrine stromal cell-derived factor −1/CXCR4 system

Abstract

Abstract We have previously demonstrated that distant metastasis might require the autocrine stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system in cases of oral squamous cell carcinoma (SCC). In this study, we examined the expression of metastasis-related genes in B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and distant metastatic potentials in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. To confirm the specificity of the microarray analysis, 3 highly upregulated genes, metabotropic glutamate receptor 5 (mGluR5), plasticity related gene 1 (PRG1), and unknown gene were reanalyzed by RT-PCR. These 3 genes were upregulated in B88-SDF-1 cells in comparison with those in mock cells, but AMD3100, a specific antagonist of CXCR4, abrogated the upregulation of 2 (mGluR5 and PRG1) out of 3 genes in B88-SDF-1 cells. Thus, we analyzed the expression of metabotropic glutamate receptor 5 (mGluR5), one of the genes that were upregulated in B88-SDF-1 cells. A specific mGluR5 antagonist, MPEP did not affect the growth of B88-SDF-1 cells, but did inhibit the enhanced-migration of B88-SDF-1 cells. When the B88-SDF-1 cells were transplanted into the vein, numerous metastatic foci were detected. Under the present conditions, MPEP significantly inhibited the lung metastasis of the B88-SDF-1 cells, ameliorated body weight loss, and improved the survival rate of tumor-bearing nude mice. These results suggested that mGluR5 might be one of a possible metastasis-related gene induced by an autocrine SDF-1/CXCR4 system in oral SCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 412.