The Effect of Radiotherapy on Cell Survival and Inflammatory Cytokine and Chemokine Secretion in a Co-Culture Model of Head and Neck Squamous Cell Carcinoma and Normal Cells

Abstract

Radiotherapy (RT) is one of the main treatments for head and neck squamous cell carcinomas (HNSCCs). Unfortunately, radioresistance is observed in many cases of HNSCCs. The effectiveness of RT depends on both the direct effect inducing cell death and the indirect effect of changing the tumor microenvironment (TME). Knowledge of interactions between TME components after RT may help to design a new combined treatment with RT. In the study, we investigated the effect of RT on cell survival and cell secretion in a co-culture model of HNSCCs in vitro. We examined changes in cell proliferation, colony formation, cell cycle phases, type of cell death, cell migration and secretion after irradiation. The obtained results suggest that the presence of fibroblasts and endothelial cells in co-culture with HNSCCs inhibits the function of cell cycle checkpoints G1/S and G2/M and allows cells to enter the next phase of the cell cycle. We showed an anti-apoptotic effect in co-culture of HNSCCs with fibroblasts or endothelial cells in relation to the execution phase of apoptosis, although we initially observed increased activation of the early phase of apoptosis in the co-cultures after irradiation. We hypothesize that the anti-apoptotic effect depends on increased secretion of IL-6 and MCP-1.

In Vitro Models of Head and Neck Cancer: From Primitive to Most Advanced

“…In the tumor in vivo microenvironment, there is an active interaction between tumor and endothelial cells, which is important for the recruitment of angiogenic cells, tumor cell survival, and migration [123,162]. In most cases, the method of co-cultivation of 2D cultures is used to analyze the interaction of tumor and endothelial cells [163]. It has been shown that exosomes produced by PCI-13 (HPV−) and UMSCC47 (HPV+) cell lines, as well as exosomes from plasma of HNSCC patients, stimulated proliferation, migration, and tube formation by human umbilical vein endothelial cells (HUVECs) in vitro and promoted formation of defined vascular structures in vivo [164].…”