P-Cadherin is Co-Expressed with Cd44 and Cd49f and Mediates Stem Cell Properties in Basal-Like Breast Cancer.
Stem Cells. 2012 Mar 2;
Authors: Vieira AF, Ricardo S, Ablett MP, Dionísio MR, Mendes N, Albergaria A, Farnie G, Gerhard R, Cameselle-Teijeiro JF, Seruca R, Schmitt F, Clarke RB, Paredes J
Abstract
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 up-regulation 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 ALDH1 in the basal subtype. Moreover, cell populations enriched for P-cadherin expression comprised increased in vitro mammosphere forming efficiency and capacity to grow colonies in 3D 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.
PMID: 22389315 [PubMed - as supplied by publisher]