Adiponectin as novel regulator of cell proliferation in human glioblastoma

J Cell Physiol. 2014 Oct;229(10):1444-54. doi: 10.1002/jcp.24582.

Abstract

Adiponectin (Acrp30) is an adipocyte-secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co-expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87-MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / pharmacology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • DNA Replication / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Adiponectin / metabolism
  • Signal Transduction / drug effects*
  • Time Factors

Substances

  • ADIPOQ protein, human
  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Adiponectin
  • Antineoplastic Agents
  • Receptors, Adiponectin
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3