Hyperthermia on mesenchymal stem cells (MSCs) can sensitize tumor cells to undergo cell death^†

Abstract

Hyperthermia, the procedure of raising the temperature of tumor-loaded tissue to 40 degrees -43 degrees C, has been applied to various established cancer treatments. Although the mechanism of hyperthermia in cancer treatment is well-known, there are few or no studies regarding the effect of hyperthermia on the tumor-supportive stroma. Mesenchymal stem cells (MSCs) display the potential for differentiation into various tissues. MSCs are also reported to play a role as potential precursors for tumor stroma in providing a favorable environment for tumor progression. Here, we investigated the effects of hyperthermia-treated MSCs on the viability and growth of cancer cells. Culture supernatants from non-shocked or heat-shocked MSCs (NS-MSCs or HS-MSCs) were added to MCF7 cells. Morphological analysis and cell proliferation assay showed the reduced viability and growth of MCF7 cells by addition of culture medium conditioned by HS-MSCs. Additionally, exposure to the conditioned medium by HS-MSCs induced cell cycle arrest at G2/M phase, increased MHC class I, Fas receptor, and TNF-R expressions, and decreased MDR1 expression in the MCF7 cells. In particular, the conditioned medium of HS-MSCs accelerated the inhibition of tumor cell growth by several chemotherapeutic drugs. These data present new aspects of hyperthermia in cancer treatment, suggesting that hyperthermia can enable tumor stroma provide a sensitizing environment for tumor cells to undergo cell death.

A study of thermal dose-induced autophagy, apoptosis and necroptosis in colon cancer cells

“…The cytotoxic effects of hyperthermia have been associated with necrotic cell death [25], induction of apoptosis [26], protein unfolding and subsequent protein aggregation [27], compromised plasma membrane [28,29] and nuclear matrix structure [30], DNA double strand breaks [31], DNA repair mechanism inhibition [32,33] and cell cycle arrest [34]. In the present study we have shown that exposing both colon cancer cell lines to increasing TD decreases cell viability.…”

Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts

“…A study demonstrated that migration of MSCs was promoted by exposure to tumor cell-conditioned medium, thus causing an increase in production of stromal cell-derived factor (SDF)-1 protein [41]; another study showed that MSCs within the tumor stroma promoted breast cancer metastasis by CCL5/CCR5 signaling [18]. Our previous studies demonstrated that cytokines secreted by MSCs can influence tumor cell growth [42,43]. Therefore, manipulation of the interaction between MSCs within the tumor stroma and tumor cells might improve conventional cancer therapy.…”

Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells

“…More importantly, a study was carried out showing that MSCs within the tumor stroma promote breast cancer metastasis by CCL5 signaling through the chemokine receptor CCR5 expressed in the tumors (18). Our previous studies demonstrated that cytokines secreted by MSCs can influence tumor cell growth (43,44). Therefore, manipulation of the interaction between MSCs within the tumor stroma and tumor cells might improve conventional cancer therapy.…”