Open Access Research article

Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

Lucia Kucerova1*, Svetlana Skolekova1, Miroslava Matuskova1, Martin Bohac23 and Zuzana Kozovska1

Author Affiliations

1 Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia

2 Department of Plastic, Aesthetic and Reconstructive Surgery, University Hospital, Bratislava, Slovakia

3 Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Bratislava, Slovakia

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BMC Cancer 2013, 13:535  doi:10.1186/1471-2407-13-535

Published: 9 November 2013

Abstract

Background

Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3.

Methods

The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed.

Results

The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil.

Conclusions

Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses.

Keywords:
Adipose tissue-derived mesenchymal stromal cells; Human breast cancer; Chemoresistance; Proliferation; Epithelial-to-mesenchymal transition; Cytokine profile