The first 2 authors contributed equally to this article.
Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line†
Article first published online: 24 DEC 2008
Copyright © 2008 American Cancer Society
Volume 115, Issue 2, pages 311–323, 15 January 2009
How to Cite
Cho, J. A., Park, H., Kim, H. K., Lim, E. H., Seo, S. W., Choi, J. S. and Lee, K. W. (2009), Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line. Cancer, 115: 311–323. doi: 10.1002/cncr.24032
- Issue published online: 7 JAN 2009
- Article first published online: 24 DEC 2008
- Manuscript Accepted: 25 AUG 2008
- Manuscript Revised: 21 AUG 2008
- Manuscript Received: 27 MAR 2008
- National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea. Grant Number: 0820250
- mesenchymal stem cells;
- tumor stroma;
- tumor microenvironment;
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°C to 43°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.
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.
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.
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. Cancer 2009. © 2009 American Cancer Society.