P-Cadherin Is Coexpressed with CD44 and CD49f and Mediates Stem Cell Properties in Basal-like Breast Cancer

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Vieira, AF (Author) Other; Ricardo, S (Author) Other; Ablett, MP (Author) Other; Dionisio, MR (Author) Other; Mendes, N (Author) Other; Albergaria, A (Author) FMUP; Farnie, G (Author) Other; Gerhard, R (Author) Other; Cameselle Teijeiro, JF (Author) Other; Seruca, R (Author) FMUP; Fernando Schmitt (Author) FMUP; Clarke, RB (Author) Other; Joana Paredes (Author) FMUP

Journal

Title: Stem Cells

Vol. 30

Pages: 854-864

ISSN: 1066-5099

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 55 Citations

Scopus - 60 Citations

Other information

Authenticus ID: P-002-AVS

DOI: 10.1002/stem.1075

Abstract (EN): 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;30:854864

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11