title: Exosomes from breast cancer cells can convert adipose tissue-derived             mesenchymal stem cells into myofibroblast-like cells.
abstract: Exosomes are small membrane vesicles secreted into the extracellular environment             by various types of cells, including tumor cells. Exosomes are enriched with a             discrete set of cellular proteins, and therefore expected to exert diverse biological             functions according to cell origin. Mesenchymal stem cells (MSCs) possess the             potential for differentiation into multilineages and can also function as precursors             for tumor stroma including myofibroblast that provides a favorable environment             for tumor progression. Although a close relationship between tumor cells and MSCs             in a neoplastic tumor microenvironment has already been revealed, how this communication             works is poorly understood. In this study, we investigated the influence of tumor             cell-derived exosomes on MSCs by treating adipose tissue-derived MSCs (ADSCs)             with breast cancer-derived exosomes. The exosome-treated ADSCs exhibited the phenotypes             of tumor-associated myofibroblasts with increased expression of α-SMA. Exosome             treatment also induced increased expression of tumor-promoting factors SDF-1,             VEGF, CCL5 and TGFβ. This phenomenon was correlated with increased expression             of TGFβ receptor I and II. Analysis of SMAD2, a key player in the TGFβ receptor-mediated             SMAD pathway, revealed that its phosphorylation was increased by exosome treatment             and was inhibited by treatment with SB431542, an inhibitor of the SMAD-mediated             pathway, resulting in decreased expression of α-SMA. Taken together, our results             show that tumor-derived exosomes induced the myofibroblastic phenotype and functionality             in ADSCs via the SMAD-mediated signaling pathway. In conclusion, this study suggests             that tumor-derived exosomes can contribute to progression and malignancy of tumor             cells by converting MSCs within tumor stroma into tumor-associated myofibroblasts             in the tumor microenvironment.
authors: Adult Stem Cell Research Institute, Department of Obstetrics                     and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School                     of Medicine, Seoul, Republic of Korea.
authors: Jung Ah
authors: JA
authors: Cho
authors: Ho
authors: H
authors: Park
authors: Eun Hye
authors: EH
authors: Lim
authors: Kyo Won
authors: KW
authors: Lee
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein