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 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. 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. Cancer 2009;115:311-23. (C) 2009 American Cancer Society.