The multifunctional G-protein-coupled metabotropic glutamate receptor (mGluR) family comprises eight subtypes, some of which participate in tumorigenesis. The purpose of this study was to evaluate mGluR5 expression in oral squamous cell carcinoma (SCC) tissues and oral cancer cell lines. We also investigated the prognostic significance of mGluR5 and its functional importance in the migration, invasion, and adhesion of oral cancer cells. We evaluated the expression of mGluR5 in samples from 131 oral SCC patients and in several oral cancer cell lines by immunohistochemistry and RT-PCR. We observed varying levels of mGluR5 in human oral SCC tissues and cancer cell lines. There was a significant association between strong mGluR5 immunoreactivity and overall survival (P=0.0109). The functional significance of the expression of mGluR5 in oral cancer cells was then investigated in HSC3 oral tongue cancer cells. An mGluR5 agonist, DHPG increased tumor cell migration, invasion, and adhesion in HSC3 cells (P<0.05). This was reversed by the mGluR5 antagonist MPEP. Our results strongly suggest that mGluR5 is a new prognostic marker and contributes to tumor cell migration and invasion in oral cancer.
BackgroundThe underlying mechanisms of carcinogenesis and gender disparity in hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) remain unclear. Recently, we reported a novel HCC-related W4P/R mutation in the large surface protein (LHB) of HBV genotype C, which was found exclusively in male HCC patients.MethodsLHB sequences from a carrier (wild type; WT) and W4P variant LHB sequence from an HCC patient were cloned and used to generate NIH3T3 and Huh7 cell lines. Cell proliferation and in vitro tumorigenicity were assessed by cell growth and transformation assays. Male and female nude mice were injected with the cells to determine in vivo tumorigenicity. To confirm the effect of estrogen in W4P-mediated tumorigenicity, male mice were injected with estrogen and challenged with W4P-expressing cells. The serum levels of different cytokines from the mouse model and patients were analyzed by ELISA. A critical role of interleukin (IL)-6 signaling in W4P-mediated tumorigenicity was tested by inhibition of Jak2.ResultsAlthough both WT and W4P variant LHBs enhanced cell proliferation by regulating the cell cycle and facilitated cell colony formation, the W4P variant demonstrated significantly higher activity. NIH3T3 cells expressing variant LHB, but not the WT, induced tumor in a nude mouse model. Tumor masses produced by variant LHB were significantly larger in male than female mice, and significantly reduced by estrogen. IL-6, but not tumor necrosis factor-α, was elevated in male mice harboring W4P-induced tumor, and was reduced by estrogen. IL-6 levels of HCC patients with the W4P variant were significantly higher than those of patients with WT LHB. W4P LHB induced higher production of IL-6 than WT LHB in cell lines, and the level was reduced by estrogen. The ability to reduce cell proliferation and colony formation of W4P LHB was hampered by inhibition of IL-6 signaling.ConclusionsThis study suggests that the W4P mutation during the natural course of chronic hepatitis B infection may contribute to HCC development, particularly in male patients, in an IL-6-dependent manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0303-7) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.