title: Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells.
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.
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia. lucia.kucerova@savba.sk.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kucerova
authors.forename: Svetlana
authors.initials: S
authors.lastname: Skolekova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Matuskova
authors.forename: Martin
authors.initials: M
authors.lastname: Bohac
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kozovska
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D019899:Paracrine Communication; D010641:Phenotype; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents