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-cadherin^high subpopulation showed higher levels of mammosphere forming efficiency (MFE) compared with P-cadherin^low cells. Additionally, the P-cadherin^high subpopulation was also enriched with cells expressing cancer stem cell surface markers, namely in CD44^high, CD24⁺ and CD49f^high 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