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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Targeting chemokine receptor CXCR7 inhibits glioma cell proliferation and mobility
Yang Liu1, Eleanor Carson-Walter2, Kevin A Walter3
1Department of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, U.S.A. yang_liu@urmc.rochester.edu kevin_walter@urmc.rochester.edu.
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.
Insights
Chemokine receptor CXCR7 promotes malignant glioma growth and invasion. Inhibiting CXCR7 in glioblastoma (GBM) cells reduced proliferation and migration, suggesting CXCR7 as a potential therapeutic target.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- The role of chemokine receptor CXCR7 in malignant brain tumors is debated.
- Understanding CXCR7's function is crucial for developing new glioblastoma therapies.
Purpose of the Study:
- To investigate the functional role of CXCR7 in glioblastoma multiforme (GBM) biology.
- To determine if CXCR7 is a viable therapeutic target for glioma.
Main Methods:
- CXCR7 expression was confirmed in clinical GBM samples and cell lines.
- Loss-of-function studies utilized small interfering RNA (siRNA) and a CXCR7 antagonist (CCX771).
- Analyzed effects on cell proliferation, invasion, migration, and ERK1/2 signaling.
Main Results:
- Higher CXCR7 levels correlated with decreased patient survival.
- CXCR7 was detected in GBM cell lines and stem-like progenitor cells.
- CXCR7 knockdown or antagonism significantly reduced glioma cell proliferation, invasion, and migration, and affected ERK1/2 signaling.
Conclusions:
- CXCR7 drives proliferation and invasion in glioma cells and stem-like cells.
- CXCR7 represents a promising therapeutic target for glioma treatment.
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