Suppression of TRPM7 Inhibits Proliferation, Migration, and Invasion of Malignant Human Glioma Cells

Abstract

BACKGROUND Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a dismal prognosis. Despite intensive study on tumor biology, the underlying mechanisms of the unlimited proliferation and progressive local invasion are still poorly understood and no effective treatment has been developed for GBM patients. AIMs We determine the role of TRPM7 channels in the growth, migration, and infiltration of malignant glioma cells. METHODS Using a combination of RT-PCR, Western blot, and patch-clamp techniques, we demonstrated the potential expression of functional TRPM7 channels in A172 cells, a human glioma cell line, as well as in human glioma tissues. Furthermore, we evaluated the role of TRPM7 in growth, migration, and infiltration in A172 cells with MTT and transwell migration and invasion assays. RESULTS We showed the expression of functional TRPM7 channels in both A172 cells and human glioma tissues. Suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration and invasion of A172 cells. Pharmacological inhibition of TRPM7 channel with 2-aminoethoxydiphenyl borate (2-APB) shows a similar effect as TRPM7-siRNA. CONCLUSION We demonstrate that human glioma cells express functional TRPM7 channel, and that activation of this channel plays an important role in the proliferation, migration and invasion of malignant glioma cells. TRPM7 channel may represent a novel and promising target for therapeutic intervention of malignant glioma.

Transient Receptor Potential Melastatin 7 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

“…There were various results in other reports, the results were controversial. Leng et al reported that suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration and invasion of glioma cells (8). Rybarczyk et al demonstrated that the down-regulation of TRPM7 by siRNA dramatically inhibited cell migration without affecting cell proliferation in pancreatic ductal adenocarcinoma cells (14).…”

“…Transient receptor potential malastatin 7 (TRPM7) is composed of a permeable Ca 2+ -Mg 2+ ion channel and an inherent serine/threonine kinase (2) and regulates many cellular processes including survival (3,4), proliferation (5-10), migration (8)(9)(10)(11)(12)(13)(14) and invasion (8). TRPM7 plays an important role in the proliferation of head and neck tumor cells (7), glioma cells (8), prostate cancer cells (9) and bladder cancer cells (10). Furthermore, TRPM7 regulates the migration of human nasopharyngeal carcinoma cells (12), breast cancer cells (13) and human pancreatic ductal adenocarcinoma cells (14).…”

Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

“…There is growing interest in understanding the role of TRPM7 overexpression and biochemical pathways implicated with proliferation, migration, and invasion of many types of cancers such as retinoblastoma [17], leukemia [18], prostate [19], and adenocarcinoma [20]. Most recently, high grade gliomas have been investigated for the overexpression of TRPM7 with special emphasis on calcium signaling [21, 22]. The present study suggests that any evaluation of TRPM7 should also include the understanding of pathological roles of elevated levels of bound Mg in high grade gliomas.…”

“…The activation of TRPM7 channel has been investigated to better understand the biochemical pathways implicated in proliferation, migration, and invasion of glioma cells with special emphasis on Ca signaling [21, 22]. Since TRPM7 is permeable to both Ca 2+ and Mg 2+ ions, and is inhibited by elevated intracellular Mg 2+ and Mg.ATP, it has been difficult to distinguish the roles of both ions in physiological and pathological conditions associated with the function of these channels [8, 23].…”

Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels

“…Glioblastoma is the most common and aggressive type of brain tumors. Recent studies suggested that both PGE2 and TRPM7 played key roles in proliferation, migration and invasion of human glioblastoma cells . Previous studies suggested that TRPM7 could be modulated by G‐protein‐coupled receptors .…”