title: Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts.
abstract: OBJECTIVE
  Most tumor tissue is composed of parenchymal tumor cells and tumor stroma. Mesenchymal stem cells (MSCs) can function as precursors for tumor stromal cells, including myofibroblasts, which provide a favorable environment for tumor progression. A close relationship between tumor cells and MSCs in a tumor microenvironment has been described. Exosomes are small membrane vesicles that are enriched with a discrete set of cellular proteins, and are therefore expected to exert diverse biological functions according to cell origin.
  
  
  METHODS
  In the current study, we determined the biological effect of exosomes from two ovarian cancer cell lines (SK-OV-3 and OVCAR-3) on adipose tissue-derived MSCs (ADSCs).
  
  
  RESULTS
  Exosome treatment induced ADSCs to exhibit the typical characteristics of tumor-associated myofibroblasts, with increased expression of α-SMA, and also increased expression of tumor-promoting factors (SDF-1 and TGF-β). This phenomenon was correlated with an increased expression of TGF-β receptors I and II. Analysis of TGF-β receptor-mediated downstream signaling pathways revealed that each exosome activated different signaling pathways, showing that exosomes from SK-OV-3 cells increased the phosphorylated form of SMAD2, which is essential in the SMAD-dependent pathway, whereas exosomes from OVCAR-3 cells increased the phosphorylated form of AKT, a representative SMAD-independent pathway. Taken together, exosomes from ovarian cancer cells induced the myofibroblastic phenotype and functionality in ADSCs by activating an intracellular signaling pathway, although the activated pathway could differ from exosome-to-exosome.
  
  
  CONCLUSIONS
  The current study suggested that ovarian cancer-derived exosomes contribute to the generation of tumor-associated myofibroblasts from MSCs in tumor stroma.
authors: 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: Kye Hyun
authors: KH
authors: Kim
authors: Joong Sub
authors: JS
authors: Choi
authors: Jung Hoon
authors: JH
authors: Lee
authors: Jae Wook
authors: JW
authors: Shin
authors: Kyo Won
authors: KW
authors: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D045744:Cell Line, Tumor; D055354:Exosomes / Q000502:physiology*; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D058628:Myofibroblasts / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D051899:Smad2 Protein / Q000502:physiology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D019869:Phosphatidylinositol 3-Kinases