P-cadherin identifies cells with stem-like properties in basal-like breast cancer


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Andre F Vieira (1), Sara Ricardo (1), Matthew Ablett (2), Raquel Seruca (3), Fernando Schmitt (3), Robert B Clarke (2), Joana Paredes (1)
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal (1), Paterson Institute for Cancer Research, Manchester, United Kingdom (2), Medical Faculty of the University of Porto, Porto, Portugal (3)

Background

P-cadherin is an adhesion molecule with a role in epithelial cell architecture, differentiation, growth, invasion and tumor progression. Breast carcinomas overexpressing P-cadherin present high histological grade and decreased cell polarity, and are associated with poor clinical outcome. There is increasing evidence that P-cadherin plays a role in stem cell biology. Our aim was therefore to establish whether P-cadherin expression confers stem cell properties to breast cancer cells.

Method

To achieve this goal, human breast cancer cell lines with different levels of P-cadherin were studied by sorting breast cancer cells using flow cytometry. Three methods for identifying putative cancer stem cells were used: i) FACS analysis for cancer stem cell surface markers, ii) determination of ALDH1 activity, and iii) culture of mammary cells in anchorage independent conditions (mammosphere assay).

Results

Basal-like breast cancer cell lines, presenting moderate to high levels of P-cadherin, show a putative stem cell population defined by ALDH1 activity, represented by 20-45% of positive cells and, in the MDA-MB-468 basal cell line, for example, the ALDEFLUOR-positive compartment was highly enriched with P-cadherin expressing cells. Furthermore, within each basal-like cell line studied, the P-cadherinhigh subpopulation showed higher levels of mammosphere forming efficiency (MFE) compared with P-cadherinlow cells. Additionally, the P-cadherinhigh subpopulation was also enriched with cells expressing cancer stem cell surface markers, namely in CD44high, CD24+ and CD49fhigh cancer cells.

Conclusion

P-cadherin expression can be a promising determinant of breast cancer stem cell activity in basal-like cell lines. In the future, we aim to test the targeting of this cell surface protein as potential therapy for basal-like breast carcinomas

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