title: Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) possess the potential for differentiation into multilineages. MSCs have been reported to play a role as precursors for tumor stroma in providing a favorable environment for tumor progression. Hyperthermia destroys cancer cells by raising the temperature of tumor-loaded tissue to 40 degrees C to 43 degrees C and causes indirect sensitizing effects when combined with chemo- and/or radiotherapy. However, how hyperthermia affects the tumor-supportive stroma is unknown. Here, the authors investigated the effects of hyperthermia-treated MSCs, from different sources, on the human ovarian cancer cell line SK-OV-3.
  
  
  METHODS
  MSCs from adipose tissue and amniotic fluid were untreated or heat-treated (HS-MSCs). The culture supernatant of each treatment group was collected and transferred to the SK-OV-3 cells.
  
  
  RESULTS
  The morphological analysis and cell proliferation assay showed a reduced viability of the tumor cells in the conditioned medium with the HS-MSCs. Further investigations revealed that the conditioned medium of the HS-MSCs induced a higher nuclear condensation and a greater number of sub-G1 cells among the tumor cells. Analysis of the mRNA expression demonstrated that the conditioned medium of the HS-MSCs induced up-regulation or down-regulation of several tumor-associated molecules. Finally, the cytokine array of each conditioned medium showed that angiogenin, insulin-like growth factor binding protein 4, neurotrophin 3, and chemokine (C-C motif) ligand 18 are involved as main factors.
  
  
  CONCLUSIONS
  This study showed that the conditioned medium of the HS-MSCs exerted a suppressive effect on tumor progression and malignancy, suggesting that hyperthermia enables tumor stromal cells to provide a sensitizing environment for tumor cells to undergo cell death.
authors.affiliation: Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Cho
authors.forename: Ho
authors.initials: H
authors.lastname: Park
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.forename: Joong Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D018929:Cell Culture Techniques; D002453:Cell Cycle; D016923:Cell Death; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006358:Hot Temperature; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D009363:Neoplasm Proteins