Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line.
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.
Cho
Jung Ah
JA
Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Park
Ho
H
Kim
Hee Kyung
HK
Lim
Eun Hye
EH
Seo
Sang Won
SW
Choi
Joong Sub
JS
Lee
Kyo Won
KW
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*
D017077:Culture Media, Conditioned; D016207:Cytokines; D009363:Neoplasm Proteins