Abstract 5329: Induction of VEGF-C expression via mGluR5 in the lymph node metastases of oral cancer by the SDF-1/CXCR4 system

Abstract

Abstract Previously, we identified a metastasis-candidate gene, metabotropic glutamate receptor (mGluR)-5, which is a target gene of stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. In this study, we examined the role of mGluR5 on the lymph node metastasis of 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 oral cancer cells, but did inhibit the SDF-1/CXCR4 dependent-migration of the cells. 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 CXCR4 expressing-oral cancer cells were transplanted into masseter muscle of nude mice, these antagonists significantly inhibited lymph node metastases of the cells. Although SDF-1/CXCR4 dependent production of angiogenic factors, including interleukin-6, interleukin-8, and vascular endothelial growth factor (VEGF)-A were observed, mGluR5 antagonists did not influence the production of these factors. However, induction of a lymphangiogenic factor, VEGF-C was specifically inhibited by the treatment with these mGluR5 antagonists. These results suggested that SDF-1/CXCR4 system induce lymph node metastases by the production of VEGF-C via upregulation of mGluR5. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5329. doi:1538-7445.AM2012-5329