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CXCR4 expression in prostate cancer progenitor cells
Authors:Dubrovska Anna  Elliott Jimmy  Salamone Richard J  Telegeev Gennady D  Stakhovsky Alexander E  Schepotin Ihor B  Yan Feng  Wang Yan  Bouchez Laure C  Kularatne Sumith A  Watson James  Trussell Christopher  Reddy Venkateshwar A  Cho Charles Y  Schultz Peter G
Institution:The Scripps Research Institute, La Jolla, California, United States of America. anna.dubrovska@oncoray.de
Abstract:Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+)/CD133(+) prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.
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