RadiosensitizationHNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity
Section snippets
Cells and cell culture
All cell lines were grown in DMEM (Gibco) supplemented with 10% fetal bovine serum (FBS) (Biochrome AG) and 2 mM glutamine (Gibco) at 37 °C, 10% CO2 and 100% humidification. HPV-positive cell lines: UT-SCC-45 (UT-45) were a kind gift from Prof. R. Grenman, Turku, Finland; UD-SCC-2 (UD-2) were a kind gift from Prof. T. Hoffmann, Essen, Germany; UM-SCC-47 (UM-47) were a kind gift from Prof. T. Carey, Michigan, USA; 93-VU-147T (93-VU) were a kind gift from Prof. J. de Winter, Amsterdam, Netherlands
Characterization of HPV-positive cell lines
The HPV-status of all cell lines utilized in this study was assessed by genomic PCR using the MY09/11 primer set. Sequencing of the respective PCR products revealed that the strains 93-VU-147T, UD-SCC-2, UM-SCC-47 and UPCI-SCC-154 contain sequences of the most abundant high-risk type HPV-16, while UT-SCC-45 cells contain sequences of a different high-risk type, HPV-33. In HPV-negative strains we additionally validated the absence of the main viral oncogenes E6 and E7 of HPV-16 (not shown),
Discussion
The aim of this project was to determine the cellular radiosensitivity of HPV/p16-positive HNSCC cell lines and to unravel the underlying mechanisms. We found that, on average, the radiosensitivity of the HPV/p16-positive cells is higher as compared to HPV-negative strains (Fig. 2B). However, both panels are characterized by considerable variation in radiosensitivity resulting in overlapping ranges of survival. This overlap may in part explain the contradictory results regarding the cellular
Conflict of interest statement
The authors declare no conflicts of interest.
Acknowledgments
The authors greatly acknowledge the technical assistance of K. Hoffer, F. Gatzemeier, T. Fritzen and B. Riepen. We further thank L. Farnebo for information on the mutational status of p53 in UT-SCC-45. This project was in part supported by Deutsche Forschungsgemeinschaft (DFG PAK 190, Di 457/8-1; E.D., M.K.).
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