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Cancer Stem Cells
Article first published online: 9 APR 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 5, pages 854–864, May 2012
How to Cite
Vieira, A. F., Ricardo, S., Ablett, M. P., Dionísio, M. R., Mendes, N., Albergaria, A., Farnie, G., Gerhard, R., Cameselle-Teijeiro, J. F., Seruca, R., Schmitt, F., Clarke, R. B. and Paredes, J. (2012), P-Cadherin Is Coexpressed with CD44 and CD49f and Mediates Stem Cell Properties in Basal-like Breast Cancer. STEM CELLS, 30: 854–864. doi: 10.1002/stem.1075
Author contributions: A.F.V.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; S.R.: collection and/or assembly of data and data analysis and interpretation; M.P.A., M.R.D., and N.M.: collection and/or assembly of data; A.A., G.F., R.G., R.S., and F.S.: data analysis and interpretation; J.F.C.-T.: provision of study material or patients; R.B.C.: conception and design, provision of study material or patients, and data analysis and interpretation; J.P.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS March 2, 2012.
- Issue published online: 9 APR 2012
- Article first published online: 9 APR 2012
- Accepted manuscript online: 2 MAR 2012 04:21PM EST
- Manuscript Accepted: 7 FEB 2012
- Manuscript Received: 16 SEP 2011
- Fundação Gulbenkian, Portugal. Grant Number: Project 96633-2010
- Programa Ciência 2007
- POPH—QREN—Tipology 4.2
- Fundação Gulbenkian
- Fundação Champalimaud, Portuguese Ministry of Science, Technology and Higher Education and FCT, Portugal
- CDH3 gene;
- Cancer stem cells;
- Basal-like breast cancer
Although the luminal progenitor cell of the normal mammary gland hierarchy has been proposed as the cell-of-origin for basal-like breast cancers, finding the cancer stem cell (CSC) phenotype for this malignancy has proven a difficult task, mostly due to the lack of specific markers. Recently, basal-like sporadic and familial cases of breast cancer have been linked to BRCA1 gene inactivation, which enables the upregulation of the target-repressed CDH3/P-cadherin gene, an important biomarker of basal-like breast carcinomas. Previously, we demonstrated that P-cadherin overexpression can mediate aggressive behavior in these tumors. Thus, our aim was to test whether P-cadherin mediates stem cell properties in basal-like breast carcinomas. Using a series of breast cancer cell lines and primary tumors, we showed that P-cadherin was directly associated with the expression of the breast stem markers CD44, CD49f, and aldehyde dehydrogenase 1 in the basal subtype. Moreover, cell population enriched for P-cadherin expression comprised increased in vitro mammosphere-forming efficiency and capacity to grow colonies in three-dimensional cultures as well as greater tumorigenicity. Importantly, an association was found with stem-/progenitor-like phenotypes of the breast, including the luminal progenitor population, CD49f+CD24+. Additionally, P-cadherin expression conferred resistance to x-ray-induced cell death, sustaining a role for this molecule in another stem cell property. In summary, we demonstrated, for the first time, that P-cadherin mediates stem cell properties, which could be explored in order to better define the CSC phenotype of basal-like breast tumors and the cell-of-origin of this malignancy. STEM CELLS 2012;30:854–864