Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

Biochem Biophys Res Commun. 2015 Feb 13;457(3):378-84. doi: 10.1016/j.bbrc.2014.12.120. Epub 2015 Jan 9.

Abstract

Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future.

Keywords: Glioblastoma; Invasion; Microgravity; Migration; SOCE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • ORAI1 Protein
  • RNA Interference
  • Stromal Interaction Molecule 1
  • Up-Regulation
  • Weightlessness Simulation*

Substances

  • Calcium Channels
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Calcium