The influence of autologous tumor fibroblasts on the radiosensitivity of squamous cell carcinoma megacolonies.
OBJECTIVE
To study the influence of tumor fibroblasts on radiosensitivity and stem cell fraction of tumor cells in squamous cell carcinoma megacolonies by determining colony cure and clonogen survival.


METHODS
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 clonogen number and the parameters of cellular radiosensitivity were calculated.


RESULTS
The curability of the co-cultured megacolonies, as determined by TCD50 values, was significantly increased compared to the megacolonies without fibroblasts (p < 0.01). Both the megacolony cure and clonogen survival data suggested a decrease of the clonogen fraction in the co-cultured megacolonies.


CONCLUSIONS
The presence of tumor fibroblasts increases megacolony radiosensitivity. This is due to a decrease in the fraction of clonogens in the tumor megacolony, apparently caused by a downregulation of the stem cell fraction of the tumor cells.
Kummermehr
J
J
Institute of Radiobiology, GSF-National Research Center for Environment and Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany. kummermehr@gsf.de
Malinen
E
E
Freykowski
S
S
Sund
M
M
Trott
K R
KR
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy*; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000528:radiation effects; D018920:Coculture Techniques; D019583:Dose Fractionation, Radiation; D005260:Female; D005347:Fibroblasts / Q000473:pathology* / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D011836:Radiation Tolerance / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000532:radiotherapy*