Oncotarget

Research Papers:

Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells

Andreas Ritter, Alexandra Friemel, Friderike Fornoff, Mouhib Adjan, Christine Solbach, Juping Yuan _ and Frank Louwen

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Oncotarget. 2015; 6:34475-34493. https://doi.org/10.18632/oncotarget.5922

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Abstract

Andreas Ritter1, Alexandra Friemel1, Friderike Fornoff1, Mouhib Adjan1, Christine Solbach1, Juping Yuan1,* and Frank Louwen1,*

1 Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Frankfurt, Germany

* These authors have equal contribution as last author

Correspondence to:

Juping Yuan, email:

Keywords: adipose-derived stem cells, breast cancer cells, epithelial-to-mesenchymal transition, invasion, drug resistance

Received: July 28, 2015 Accepted: September 08, 2015 Published: September 30, 2015

Abstract

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.


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