Abstract 2279: The oncogenic role of TRPM7 in cell proliferation and invasion of U87MG glioma cells

Abstract

Abstract Background: We have previously reported that suppression of TRPM7 channels inhibit proliferation, migration, and invasion of malignant human glioma cells (CNS Neuroscience & Therapeutics, in press) using A172 glioma cell line and brain tissue of human glioma. By studying glioma cancer stem cells derived from A172 cells, we further found that TRPM7 channels regulate glioma stem cell growth/proliferation through STAT3 and Notch signaling pathways (Cellular Signaling, 2014; 26: 2773-2781). However, the genetic difference of in vitro cell lines mirrors the diversity of individual patient cases. For instance, Ke et al reported that the differences in tumorigenicity among the different glioma cell lines were associated with the expression levels of bFGF and/or VEGF, two potent angiogenic factors in gliomas (Clin Cancer Res 2000; 6: 2562-2572). Interestingly, A172 cells produce a high-level bFGF, while U87MG cells secrete a significantly higher level of VEGF than other glioma cells. To determine whether our previous findings are not limited to A172 cells, we examined the role of TRPM7 channels in aforementioned malignant features of U87MG cells as well. We hypothesize that TRPM7 promotes proliferation and invasion in U87MG glioma cells. Methods: 1) We examined TRPM7-like current using patch-clamp technique in U87MG glioma cells. 2) We examined the TRPM7 mRNA and protein expression using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot respectively. 3) We determined the effects of TRPM7 on glioma cell proliferation and invasion using MTT assay and transwell invasion assay respectively by downregulating TRPM7 expression using siTRPM7 and inhibiting TRPM7 function using 2-APB, a non-specific pharmacological inhibitor. Results: 1) Electrophysiological recording showed a TRPM7-like current induced by Ca2+ and Mg2+ removal, which suggested that TRPM7 channels also exist in U87MG cells. 2) PCR and Western blot showed that U87MG cells express TRPM7 mRNA and protein. 3) Treatment of U87MG cells with siTRPM7 significantly reduced TRPM7 expression. 4) The cell proliferation and invasion were significantly reduced when treated with siTRPM7 and 2-APB which indicate that TRPM7 promotes growth and invasion of U87MG cells. 5) Inhibition of TRPM7 activity blocked calcium induced cell proliferation further indicating that TRPM7 activity is required for cell proliferation. Conclusion: TRPM7 promotes proliferation and invasion of U87MG glioma cells. TRPM7 may play a generalized role in glioma initiation and progression and might be an important drug target of glioma. (This work is supported by R01NS066027, NIMHD S21MD000101, U54NS08932, and AHA 0840132.) Citation Format: Mingli Liu. The oncogenic role of TRPM7 in cell proliferation and invasion of U87MG glioma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2279. doi:10.1158/1538-7445.AM2015-2279