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Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
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Published on: October 20, 2016

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Phospho-mTOR expression in human glioblastoma microglia-macrophage cells

Lucia Lisi1, Gabriella Maria Pia Ciotti1, Marta Chiavari1

  • 1Institute of Farmacologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy.

Neurochemistry International
|June 14, 2019
PubMed

Insights

Targeting mTOR signaling in glioblastoma (GBM) may reduce M2-polarized microglia, a pro-tumorigenic phenotype. This suggests mTOR inhibitors could offer additional anti-cancer effects beyond direct tumor cell impact.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Cancer Biology

Background:

  • Glioblastoma (GBM) features a heterogeneous immune microenvironment, with microglia comprising a significant portion of tumor cells.
  • The precise roles of microglia and other immune cells in GBM are not fully understood.
  • Mammalian target of rapamycin (mTOR) signaling is implicated in cancer and microglia-glioma cell interactions.

Purpose of the Study:

  • To investigate the activation status of mTOR signaling in tumor-associated microglia (TAMs) within human GBM specimens.
  • To examine the effect of mTOR inhibition on the M2 phenotype of microglia in a human microglia-glioma interaction model.

Main Methods:

  • Analysis of human GBM tumor specimens (n=42) for phosphorylated mTOR (Ser-2448) expression in TAMs.
  • Utilizing a human microglia-glioma co-culture system to study mTOR activation and M2 marker expression (urea, ARG1).
  • Assessing the impact of an mTOR inhibitor on microglial M2 phenotype expression.

Main Results:

  • Approximately 39% of TAMs in human GBM specimens exhibited activated mTOR signaling (p-mTOR Ser-2448).
  • Similar mTOR activation was observed in the human microglia-glioma interaction model.
  • Microglia expressed M2 markers (urea, ARG1) in the presence of glioma cells, which was reduced by mTOR inhibition.

Conclusions:

  • mTOR pathway activation is present in a substantial subset of TAMs in human GBM.
  • mTOR inhibition may decrease the M2 phenotype in TAMs, potentially impacting up to 40% of these cells.
  • Reducing the M2 microglial phenotype could be an additional anti-tumor mechanism for mTOR inhibitors in GBM treatment.
Keywords:
GlioblastomaMicrogliaMolecularly targeted therapiesTSC2Tumor microenvironmentmTOR

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