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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

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

Revista

Título: Stem Cells

Vol. 30

Páginas: 854-864

ISSN: 1066-5099

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 55 Citações

Scopus - 60 Citações

Outras Informações

ID Authenticus: 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

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11