Interaction of head and neck squamous cell carcinoma cells and mesenchymal stem cells under hypoxia and normoxia

Abstract

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.

Similarities between Tumour Immune Response and Chronic Wound Microenvironment: Influence of Mesenchymal Stromal/Stem Cells

“…Similarly, in in vitro studies when MSCs were cocultured with a head and neck squamous cell carcinoma cell line (FaDu), cancer cell viability and proliferation decreased when incubated in conditioned media that was derived from MSCs grown under hypoxic conditions. Levels of anti-inflammatory cytokines such as IL-4, IL-5, and IL-10 are reduced, and IL-6 is increased in this conditioned medium [97]. This data suggests that despite the fact that MSCs are expanded under normoxic conditions, they may reestablish homeostasis in the hypoxic TME and still have an effect on cancer cells.…”

The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors

“…In short, the bi-interactions between MSCs and tumor cells have been proposed to play a critical role in the growth, survival, metastasis and drug resistance of solid tumors (62,63). But tumor cells alone do not cause the naïve MSCs to acquire all of the features displayed by CA-MSCs (33), indicating the participation of other mediators or factors from the TME in "shaping" the phenotypes and functions of CA-MSCs.…”

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma

“…Therefore, MSC-based treatments for cancer patients suffering from radiotherapy-induced toxicities are still controversially discussed. Only a few studies have analyzed the interaction between MSCs and HNSCCs in the context of cancer progression, hypoxia, and drug resistance, and there is to the best of our knowledge no study in which the risk for MSC-mediated radioprotection of HNSCCs has been investigated [ 28 , 29 , 30 ].…”