The goal of this work was to clarify the effect of carbon-ion beams on reduction of the metastatic potential of malignant melanoma using in vitro and in vivo techniques. We utilized a 290 MeV/u carbon beam with a 6-cm spread-out Bragg-peak (SOBP), 137Cs γ rays or 200 kVp X rays for irradiation, and in vitro murine melanoma B16/BL6 cells that were implanted into C57BL/6J mice. The metastatic abilities (migration, invasion and adhesion) were suppressed by carbon ion treatment at all doses that were tested, whereas invasion and migration tended to increase after X-ray irradiation at low dose. Biological effects of carbon ions increased with linear energy transfer (LET) for both cell killing and metastatic abilities, although the effects were more pronounced for migration and invasion. mRNA expression of E-cadherin was significantly downregulated with low-dose photon exposures, but increased with dose or LET. Expression of Mel-CAM and L1-CAM was upregulated after low-dose photon exposure, but decreased with dose, especially after carbon-ion treatment. Conversely, these molecules showed a reversal in expression changes, especially after low-dose photon exposure. Cell-cell adhesion may be an important contributor to the antimetastatic effect of carbon ion treatment. The number of lung metastases after local tumor irradiation significantly decreased with increased dose and LET, with carbon ions being more effective than γ rays. Integrating dose-response curves to examine the relationship between cell killing and lung metastasis clearly showed that carbon ions inhibit lung metastasis more efficiently than photons at the iso-effective level of cell killing. Thus, carbon ions were more effective than photon beams, not only at killing tumor cells, but also at inhibiting metastatic spread caused by tumor cells that survived irradiation.
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1 October 2018
REGULAR ARTICLES|
July 24 2018
Antimetastatic Effects of Carbon-Ion Beams on Malignant Melanomas
Yoshitaka Matsumoto;
Yoshitaka Matsumoto
1
aRadiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
bProton Medical Research Center, University of Tsukuba Hospital, Tsukuba, 305-8576, Japan
1Address for correspondence: Radiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8576, Japan; email: ymatsumoto@pmrc.tsukuba.ac.jp.
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Yoshiya Furusawa;
Yoshiya Furusawa
cDepartment of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan
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Akiko Uzawa;
Akiko Uzawa
dDepartment of Charged Particle Therapy Research, Clinical Research Cluster, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan
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Ryoichi Hirayama;
Ryoichi Hirayama
dDepartment of Charged Particle Therapy Research, Clinical Research Cluster, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan
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Sachiko Koike;
Sachiko Koike
eDepartment of Accelerator and Medical Physics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan
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Koichi Ando;
Koichi Ando
fMedicine & Biology Division, Heavy Ion Medical Center, Gunma University, Gunma, 371-8511, Japan
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Koji Tsuboi;
Koji Tsuboi
aRadiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
bProton Medical Research Center, University of Tsukuba Hospital, Tsukuba, 305-8576, Japan
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Hideyuki Sakurai
Hideyuki Sakurai
aRadiation Oncology, Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
bProton Medical Research Center, University of Tsukuba Hospital, Tsukuba, 305-8576, Japan
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Radiat Res (2018) 190 (4): 412–423.
Article history
Received:
March 05 2018
Accepted:
June 26 2018
Citation
Yoshitaka Matsumoto, Yoshiya Furusawa, Akiko Uzawa, Ryoichi Hirayama, Sachiko Koike, Koichi Ando, Koji Tsuboi, Hideyuki Sakurai; Antimetastatic Effects of Carbon-Ion Beams on Malignant Melanomas. Radiat Res 1 October 2018; 190 (4): 412–423. doi: https://doi.org/10.1667/RR15075.1
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