Abstract 2440: Inhibition of SDF-1/CXCR4 dependent-metastases by the treatment with metabotropic glutamate receptor 5 (mGluR5) antagonists in oral cancer

Previously, we identified a metastasis-candidate gene, metabotropic glutamate receptor (mGluR)-5 by using an oral cancer cell line, B88-SDF-1, which have an autocrine stromal cell-derived factor (SDF)-1/CXCR4 system and distant metastatic potentials in vivo. In this study, we examined the effect of mGluR5 antagonists on the SDF-1/CXCR4 dependent-metastases in oral cancer. We used 2 kinds of mGluR5-specific antagonists, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP). These antagonists did not affect the growth of B88-SDF-1 cells, but did inhibit the enhanced-migration of the cells. Under these conditions, actin polymerization and pseudopodia formation were also inhibited by the treatment with MPEP and MTEP. In order to confirm the drug toxicities, these antagonists were intraperitoneally injected into wild-type mice for 4 weeks. All the mice injected with MPEP (5 mg/kg) and MTEP (5 mg/kg) did not show side effects, such as hematotoxicity, allergic reaction and body weight loss. When the B88-SDF-1 cells were transplanted into the vein of nude mice, these antagonists significantly inhibited the lung metastases of the cells. These results suggested that blockade of mGluR5, using antagonists such as MPEP and MTEP, may be effective at preventing metastasis in patients with CXCR4-related oral cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2440. doi:10.1158/1538-7445.AM2011-2440