Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature |
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Authors: | George J. Klarmann Elaine M. Hurt Lesley A. Mathews Xiaohu Zhang Maria A. Duhagon Tashan Mistree Suneetha B. Thomas William L. Farrar |
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Affiliation: | (1) Cancer Stem Cell Section, Laboratory of Cancer Prevention, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702, USA;(2) Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles St., Building 560, Room 21-81, Frederick, MD 21702, USA;(3) LIM-F. Ciencias, Igua 4225, Universidad de la República, CP 11400/Genetica-F. Medicina, Gral. Flores 2125, CP 11800, Montevideo, Uruguay |
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Abstract: | Development of metastasis is a leading cause of cancer-induced death. Acquisition of an invasive tumor cell phenotype suggests loss of cell adhesion and basement membrane breakdown during a process termed epithelial-to-mesenchymal transition (EMT). Recently, cancer stem cells (CSC) were discovered to mediate solid tumor initiation and progression. Prostate CSCs are a subpopulation of CD44+ cells within the tumor that give rise to differentiated tumor cells and also self-renew. Using both primary and established prostate cancer cell lines, we tested the assumption that CSCs are more invasive. The ability of unsorted cells and CD44-positve and -negative subpopulations to undergo Matrigel invasion and EMT was evaluated, and the gene expression profiles of these cells were analyzed by microarray and a subset confirmed using QRT-PCR. Our data reveal that a subpopulation of CD44+ CSC-like cells invade Matrigel through an EMT, while in contrast, CD44− cells are non-invasive. Furthermore, the genomic profile of the invasive cells closely resembles that of CD44+CD24− prostate CSCs and shows evidence for increased Hedgehog signaling. Finally, invasive cells from DU145 and primary prostate cancer cells are more tumorigenic in NOD/SCID mice compared with non-invasive cells. Our data strongly suggest that basement membrane invasion, an early and necessary step in metastasis development, is mediated by these potential cancer stem cells. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Cancer stem cells Metastasis Invasion EMT Prostate cancer Hedgehog |
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