Application of Carbon Ion Beams or Gamma-Rays on Primary Tumors Does Not Change the Expression Profiles of Metastatic Tumors in an in vivo Murine Model

Purpose: To clarity how carbon-ion radiotherapy on primary tumors affects the characteristics of subsequently-arising metastatic tumor cells.Methods and Materials: Mouse squamous cell carcinomas, NR-S1, in synergic C3H/HeMsNrs mice were irradiated with a single dose of 5-50 Gy of carbon-ions (C-ion) (290 MeV/nucleon, 6 cm spread-out Bragg peak) or gamma-rays (GAMMA-rays) (137Cs source) as a reference beam. The volume of the primary tumors and the number of metastatic nodules in lung were studied, and histological analysis and microarray analysis of laser-microdissected tumor cells were also performed.Results: Including 5 Gy of C-ion and 8 Gy of GAMMA-rays, which did not inhibit the primary tumor growth, all doses used in this study inhibited lung metastasis significantly. Pathological findings showed no difference among the metastatic tumor nodules in the non-irradiated, carbon-ion-irradiated, and GAMMA- ray-irradiated groups. Clustering analysis of expression profiles among metastatic tumors and primary tumors revealed a single cluster consisting of metastatic tumors different from their original primary tumors, indicating that the expression profiles of the metastatic tumor cells were not affected by the local application of C-ion radiotherapy or GAMMA-ray radiotherapy.Conclusion: We found no difference in the incidence and histology, and only small differences in expression profile, of distant metastasis between local C-ion and GAMMA-ray radiotherapy. The application of local radiotherapy per se or the type of radiotherapy applied did not influence the transcriptional changes caused by metastasis in tumor cells