The radioresistance of clinically relevant radioresistant cell-derived tumors is determined by the cancer cells themselves, rather than by the surrounding stromal cells.

Background/purpose: We established clinically relevant radioresistant (CRR) cell lines, which proliferate after exposure to 2 Gy/day of X-rays with the same genomic background as the parental cell lines from SAS cells, a cell line derived from oral squamous cell carcinoma. In this study, we tried to analyze whether the radioresistance of the tumor is defined by the stromal cells or the cancer cells using the CRR cells. Materials and methods: We transplanted parental and CRR cells into nude mice. The effects of 2 Gy/day fractionated radiation (FR) on the tumors were observed for 30 days. We measured tumor size, nuclear size by Hematoxylin-Eosin staining, Ki-67 expression via immunostaining, and Autophagosome formation using Electron microscopy. Results: From the 20th day of FR, the SAS tumor volume gradually decreased. At 30 days of FR, the SAS tumor volume was reduced by half. Conversely, SAS-R tumors maintained a constant level after FR. The histology of the SAS tumor exhibited advanced fibrosis and enlarged cell nuclei. However, the SAS-R tumor showed no notable fibrosis, and the cell nuclei in the SAS-R tumors were like the nonirradiated cells. The number of Ki-67 positive cells was reduced in SAS tumors but not SAS-R tumors. Electron microscopy revealed autophagosome-like structures in the parent cells, but not in the SAS-R cells. Conclusion: The cancer cells themselves define the radioresistance of the tumor rather than by the surrounding stromal cells.