Article
Comparison of the Effect of Gamma-Ray and Carbon-Ion Radiotherapy on Metastasis in an In Vivo Murine Model
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Published: | September 24, 2009 |
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Purpose: To clarify how carbon-ion radiotherapy (C-ion) on primary tumors affects the characteristics of subsequently arising metastatic tumor cells.
Materials and methods: Mouse squamous cell carcinomas, NR-S1, in synergic C3H/HeMsNrs mice were irradiated with a single dose of 5–50 Gy of C-ion (290 MeV per nucleon, 6-cm spread-out Bragg peak) or g-rays (137Cs source) as a reference beam. The volume of the primary tumors and the number of metastatic nodules in lung were studied, and histologic analysis and microarray analysis of laser-microdissected tumor cells were also performed.
Results: Including 5 Gy of C-ion and 8 Gy of g-rays, which did not inhibit the primary tumor growth, all doses used in this study inhibited lung metastasis significantly. Pathologic findings showed no difference among the metastatic tumor nodules in the non-irradiated, C-ion-irradiated, and g-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 or g-ray radiotherapy. However, the difference of transcriptional profiles between lung metastases after local radiotherapy with C-ion and g-rays was also found in our study. The genes whose expression differed between the primary tumors and the metastatic tumors included Kit and MMP8, while the genes whose expression differed between the lung metastases after g-ray and C-ion radiotherapy included S100a8 and S100a9.
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 g-ray radiotherapy. The application of local radiotherapy per se or the type of radiotherapy applied did not significantly influence the transcriptional changes caused by metastasis in tumor cells.