Targeting Chemokine Receptor CXCR7 Inhibits Glioma Cell Proliferation and Mobility

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.