Adipose-derived stem cells are capable of differentiating into multiple cell types and thus considered useful for regenerative medicine. However, this differentiation feature seems to be associated with
tumor initiation and
metastasis raising safety concerns, which requires further investigation. In this study, we isolated adipose-derived stem cells from subcutaneous as well as from visceral adipose tissues of the same donor and systematically compared their features. Although being characteristic of mesenchymal stem cells, subcutaneous adipose-derived stem cells tend to be spindle form-like and are more able to home to
cancer cells, whereas visceral adipose-derived stem cells incline to be "epithelial"-like and more competent to differentiate. Moreover, compared to subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are more capable of promoting proliferation, inducing the epithelial-to-mesenchymal transition, enhancing migration and invasion of
breast cancer cells by cell-cell contact and by secreting
interleukins such as
IL-6 and
IL-8. Importantly, ASCs affect the low malignant
breast cancer cells MCF-7 more than the highly metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal transition is mediated by the activation of multiple pathways especially the PI3K/AKT signaling in
breast cancer cells. BCL6, an important player in
B-cell lymphoma and
breast cancer progression, is crucial for this transition. Finally, this transition fuels malignant properties of
breast cancer cells and render them resistant to
ATP competitive
Polo-like kinase 1 inhibitors BI 2535 and
BI 6727.