Suppression of TRPM7 inhibits proliferation, migration, and invasion of malignant human glioma cells

CNS Neurosci Ther. 2015 Mar;21(3):252-61. doi: 10.1111/cns.12354. Epub 2014 Dec 1.

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 expression of functional TRPM7 channels of 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 of 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) showed 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.

Keywords: Glioma; Invasion; Migration; Proliferation; TRPM7.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Boron Compounds / pharmacology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / physiopathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Glioblastoma / drug therapy
  • Glioblastoma / physiopathology*
  • Humans
  • Neoplasm Invasiveness / physiopathology*
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • TRPM Cation Channels / antagonists & inhibitors*
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism

Substances

  • Boron Compounds
  • RNA, Messenger
  • RNA, Small Interfering
  • TRPM Cation Channels
  • 2-aminoethoxydiphenyl borate
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human