Integrin αv expression is required for the acquisition of a metastatic stem/progenitor cell phenotype in human prostate cancer.

Abstract	Integrins participate in multiple cellular processes, including cell adhesion, migration, proliferation, survival, and the activation of growth factor receptors. Recent studies have shown that expression of αv integrins is elevated in the prostate cancer stem/progenitor cell subpopulation compared with more differentiated, committed precursors. Here, we examine the functional role of αv integrin receptor expression in the acquisition of a metastatic stem/progenitor phenotype in human prostate cancer. Stable knockdown of αv integrins expression in PC-3M-Pro4 prostate cancer cells coincided with a significant decrease of prostate cancer stem/progenitor cell characteristics (α2 integrin, CD44, and ALDH(hi)) and decreased expression of invasion-associated genes Snail, Snail2, and Twist. Consistent with these observations, αv-knockdown strongly inhibited the clonogenic and migratory potentials of human prostate cancer cells in vitro and significantly decreased tumorigenicity and metastatic ability in preclinical models of orthotopic growth and bone metastasis. Our data indicate that integrin αv expression is functionally involved in the maintenance of a highly migratory, mesenchymal cellular phenotype as well as the acquisition of a stem/progenitor phenotype in human prostate cancer cells with metastasis-initiating capacity.
Authors	Christel van den Hoogen, Geertje van der Horst, Henry Cheung, Jeroen T Buijs, Rob C M Pelger, Gabri van der Pluijm
Journal	The American journal of pathology (Am J Pathol) Vol. 179 Issue 5 Pg. 2559-68 (Nov 2011) ISSN: 1525-2191 [Electronic] United States
PMID	21907176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Chemical References	Biomarkers, Tumor Integrin alphaV
Topics	Animals Biomarkers, Tumor (metabolism) Cell Line, Tumor Cell Movement Cell Transformation, Neoplastic (metabolism) Gene Knockdown Techniques Humans Integrin alphaV (metabolism) Male Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Neoplastic Stem Cells (metabolism) Phenotype Prostatic Neoplasms (metabolism) Tumor Stem Cell Assay Up-Regulation

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