title: Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells.
abstract: BACKGROUND
  Cells of the tumor microenvironment are recognized as important determinants of the tumor biology. The adjacent non-malignant cells can regulate drug responses of the cancer cells by secreted paracrine factors and direct interactions with tumor cells.
  
  
  RESULTS
  Human mesenchymal stromal cells (MSC) actively contribute to tumor microenvironment. Here we focused on their response to chemotherapy as during the treatment these cells become affected. We have shown that the secretory phenotype and behavior of mesenchymal stromal cells influenced by cisplatin differs from the naïve MSC. MSC were more resistant to the concentrations of cisplatin, which was cytotoxic for tumor cells. They did not undergo apoptosis, but a part of MSC population underwent senescence. However, MSC pretreatment with cisplatin led to changes in phosphorylation profiles of many kinases and also increased secretion of IL-6 and IL-8 cytokines. These changes in cytokine and phosphorylation profile of MSC led to increased chemoresistance and stemness of breast cancer cells.
  
  
  CONCLUSIONS
  Taken together here we suggest that the exposure of the chemoresistant cells in the tumor microenvironment leads to substantial alterations and might lead to promotion of acquired microenvironment-mediated chemoresistance and stemness.
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia. svetlana.skolekova@savba.sk.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Skolekova
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia. miroslava.matuskova@savba.sk.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Matuskova
authors.affiliation: Department of Plastic, Aesthetic and Reconstructive Surgery, University Hospital, Bratislava, Slovakia. bohac.md@gmail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Bohac
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia. exonbara@savba.sk.
authors.forename: Lenka
authors.initials: L
authors.lastname: Toro
authors.forename: Erika
authors.initials: E
authors.lastname: Durinikova
authors.forename: Silvia
authors.initials: S
authors.lastname: Tyciakova
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovakia. lucia.demkova@savba.sk.
authors.forename: Lucia
authors.initials: L
authors.lastname: Demkova
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, Olomouc, Czech Republic. jan.gursky@upol.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Gursky
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
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D002945:Cisplatin