Pre-Irradiated Fibroblasts Influence the Chemosensitivity of Co-Cultivated Squamous Cell Carcinoma Cells

Objective: Tumor stroma mainly consists of fibroblasts, which have a multitude of interactions with the cancer cells they surround. Since irradiation and chemotherapy are common therapeutic options for squamous cell carcinoma of the head and neck, the effects of irradiation on tumor stroma and their sensitivity to chemotherapeutic agents are of significant therapeutic interest. Methods: FaDu head and neck squamous cell carcinoma cells (HNSCC) were cultivated with fibroblasts from pre-irradiated and non-irradiated human skin for 24 hours. Then the co-cultures were treated with either Cisplatin, Paclitaxel or 5-Fluorouracil for 48 hours. Analysis of tumor viability and apoptosis were conducted via the MTT assay and the Annexin V-propidium iodide test. Secretion of interleukin-8 (IL-8) was analyzed with an enzyme-linked immunosorbent assay. Results: Co-cultures with pre-irradiated fibroblasts showed decreased viability, higher rates of apoptosis and necrosis, and lower levels of IL-8 as compared to co-cultures with non-irradiated fibroblasts in the presence of chemotherapeutic agents as well as in the control group. Conclusion: We therefore postulate an influence of a previous irradiation of fibroblasts on the chemosensitivity of co-cultured tumor cells. To achieve a better understanding of the effects of cytostatic treatment in pre-irradiated head and neck cancer patients, further investigations are warranted.