CXCR4 expression in prostate cancer progenitor cells

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 regu...

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Bibliographic Details
Published in:PloS one 2012-02, Vol.7 (2), p.e31226-e31226
Main 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
Format: Article
Language:English
Subjects:
Androgens
Animals
Antineoplastic Combined Chemotherapy Protocols
Biology
Breast cancer
Bulk drugs
Cancer
Cancer metastasis
Cancer research
Cancer therapies
CD44 antigen
Cell Adhesion
Cell adhesion & migration
Cell differentiation
Cell Proliferation
Cells (biology)
Chemokine CXCL12 - metabolism
Chemokines
Chemotherapy
CXCL12 protein
CXCR4 protein
Development and progression
Docetaxel
Drug resistance
Gene expression
Genomics
Heterocyclic Compounds - pharmacology
Humans
Kinases
Leukemia
Male
Medical prognosis
Medicine
Metastases
Metastasis
Mice
Neoplasm Metastasis
Neoplastic Stem Cells - metabolism
Population
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Receptors, CXCR4 - metabolism
Rodents
Stem cells
Taxoids - pharmacology
Taxotere
Tumorigenicity
Tumors
Xenografts
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0031226