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.
OBJECTIVE
To clarify how carbon-ion radiotherapy (C-ion) on primary tumors affects the characteristics of subsequently arising metastatic tumor cells.


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 gamma-rays ((137)Cs 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 gamma-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 nonirradiated, C-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 or gamma-ray radiotherapy.


CONCLUSIONS
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.
RadGenomics Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
Tomoaki
T
Tamaki
Mayumi
M
Iwakawa
Tatsuya
T
Ohno
Kaori
K
Imadome
Miyako
M
Nakawatari
Minako
M
Sakai
Hirohiko
H
Tsujii
Takashi
T
Nakano
Takashi
T
Imai
D000818:Animals; D002250:Carbon Radioisotopes / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D005720:Gamma Rays / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012334:RNA, Neoplasm / Q000302:isolation & purification; D011879:Radiotherapy Dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D047368:Tumor Burden
D002250:Carbon Radioisotopes; D012334:RNA, Neoplasm