The influence of autologous tumor fibroblasts on the radiosensitivity of squamous cell carcinoma megacolonies

Purpose: To study the influence of tumor fibroblasts on radiosensitivity an d stem cell fraction of tumor cells in squamous cell carcinoma megacolonies by determining colony cure and clonogen survival, Methods and Materials: Murine squamous cell carcinoma cells (AT478c) grown as flat but multilayered megacolonies were co-cultured with pre-irradiated tumor fibroblasts derived from the same carcinoma, and irradiated with 1, 2 , 4, or 8 fractions. Recurrent clones and their growth pattern in situ were recorded. From megacolony cure data and clonogen survival data, the clonog en number and the parameters of cellular radiosensitivity were calculated, Results: The curability of the co-cultured megacolonies, as determined by T CD50 values, was significantly increased compared to the megacolonies witho ut fibroblasts (p < 0.01). Both the megacolony cure and clonogen survival d ata suggested a decrease of the clonogen fraction in the so-cultured megaco lonies, Conclusion: The presence of tumor fibroblasts increases megacolony radiosen sitivity. This is due to a decrease in the fraction of clonogens in the tum or megacolony, apparently caused by a downregulation of the stem cell fract ion of the tumor cells, (C) 2001 Elsevier Science Inc.