Differences in tumor stroma derived from irradiated versus non-irradiated fibroblasts in a co-culture model with head and neck squamous cell carcinoma

Abstract

Cancer cells have a variety of interactions with neighboring connective tissue, and this activity primarily involves fibroblasts. Co-culture of fibroblasts derived from human skin with cancer cells results in the conversion of fibroblasts into cancer-associated fibroblasts, which are known to support tumor growth and invasiveness. To evaluate the effect of radiation on tumor-fibroblast interactions, the present study co-cultivated fibroblasts from pre-irradiated and non-irradiated human skin with FaDu head and neck squamous cell carcinoma cells for 3 days. Subsequently, cells were analyzed for tumor viability, apoptosis, and secretion of interleukin (IL)-6 and -8 by performing an MTT assay, Annexin V-propidium iodide test and enzyme-linked immunosorbent assay, respectively. Co-culture of FaDu cells with pre-irradiated fibroblasts resulted in a significant decrease in tumor viability, a notable increase in apoptosis and significantly lower levels of IL-8 compared with FaDu cells cultured with non-irradiated fibroblasts. Therefore, we propose that pre-irradiation changes the properties of fibroblasts and their effects on co-cultivated tumor cells, and, thus may lead to an improved understanding of the therapeutic options for patients that have already undergone irradiation.