title: 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: Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Christel
authors: C
authors: van den Hoogen
authors: Geertje
authors: G
authors: van der Horst
authors: Henry
authors: H
authors: Cheung
authors: Jeroen T
authors: JT
authors: Buijs
authors: Rob C M
authors: RC
authors: Pelger
authors: Gabri
authors: G
authors: van der Pluijm
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D039564:Integrin alphaV