Targeting chemokine receptor CXCR7 inhibits glioma cell proliferation and mobility

Anticancer Res. 2015 Jan;35(1):53-64.

Abstract

Background: The functional contribution of chemokine receptor CXCR7 to malignant brain tumor biology remains controversial.

Materials and methods: Complementary methods were used to confirm CXCR7 expression in clinical glioblastoma multiforme (GBM) specimens and multiple GBM cell lines. Loss-of-function studies were performed using small interfering RNA (siRNA) technology.

Results: Elevated CXCR7 levels correlated with reduced survival in glioma patients. CXCR7 was expressed by GBM cell lines and stem-like progenitor cells. Knockdown of CXCR7 by siRNA attenuated phosphorylation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway in response to CXCL12 and resulted in significantly reduced cell proliferation, invasion and migration. Similarly, treatment of glioma cells with a small molecule antagonist of CXCR7, CCX771, significantly inhibited cell proliferation and invasion.

Conclusion: CXCR7 actively promotes the proliferation and invasive behavior of glioma tumor cells and stem-like progenitor cells and may be a potential target for glioma therapy.

Keywords: CXCL12; CXCR7; glioma; mobility; proliferation.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Chemokine CXCL12 / physiology
  • Drug Screening Assays, Antitumor
  • Gene Knockdown Techniques
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / physiology
  • Receptors, CXCR / antagonists & inhibitors
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism*

Substances

  • ACKR3 protein, human
  • Antineoplastic Agents
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR