CXCR4 expression in prostate cancer progenitor cells

PLoS One. 2012;7(2):e31226. doi: 10.1371/journal.pone.0031226. Epub 2012 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Adhesion
  • Cell Proliferation
  • Chemokine CXCL12 / metabolism
  • Docetaxel
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Male
  • Mice
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, CXCR4 / metabolism*
  • Taxoids / pharmacology

Substances

  • CXCR4 protein, human
  • Chemokine CXCL12
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • Taxoids
  • Docetaxel
  • plerixafor octahydrochloride