Mesenchymal stem cells (MSCs) exhibit strong tropism towards tumor tissue. While MSCs generally surround tumors, they can also infiltrate tumors and thereby influence their proliferation. Interactions between MSCs and tumor cells are usually tested under normoxia, but the majority of solid tumors, including head and neck squamous cell carcinoma (HNSCC), are also characterized by hypoxic areas. Hence, the present study aimed to assess the interaction between MSCs and tumor cells under hypoxic conditions. MSCs were cultivated under normoxia and hypoxia, and conditioned media were used to cultivate the HNSCC cell line FaDu. The cell cycle distribution and viability of MSCs and the proliferation of FaDu cells were analyzed under normoxia and hypoxia, and changes in cytokine levels in the conditioned media were evaluated. No cell cycle changes were observed for MSCs after 24 h of cultivation under hypoxia, but the cell viability had declined. Hypoxia also led to a decrease in the proliferation of FaDu cells; however, FaDu cells proliferated faster after 48 h under hypoxia compared with normoxic conditions. This effect was reversed after incubation under normoxia for 72 h and hypoxia for 72 h. While these changes constituted a trend, these differences were not statistically significant. A cytokine assay showed an increase in interleukin (IL)-6 in the hypoxic medium. Overall, the results indicated that there was an interaction between MSCs and tumor cells. The presence or absence of oxygen seemed to influence the functionality of MSCs and their protumorigenic properties, in which IL-6 was identified as a potential mediator. Since MSCs are a component of the tumor stroma, further in vitro and in vivo studies are needed to investigate this interaction in order to develop novel approaches for tumor therapy.
Keywords: FaDu; cell cycle; head and neck squamous cell carcinoma; hypoxia; interleukin-6; mesenchymal stem cells; normoxia; proliferation.
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