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Particle Irradiation Suppresses Metastatic Potential of Cancer Cells

Departments of ¹ Medical Physics & Engineering and ² Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; ³ Department of Radiology, Hyogo Ion Beam Medical Center, Ibo-gun, Hyogo, Japan; and Laboratories of ⁴ International Space Radiation; and ⁵ Heavy-ion Radiobiology for Therapy, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan

Requests for reprints: Teruki Teshima, Departments of Medical Physics & Engineering, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 166-879-2570; Fax: 166-879-2570; E-mail: teshima{at}sahs.med.osaka-u.ac.jp.

Particle radiotherapy such as proton and carbon ion has been producing promising clinical results worldwide. The purpose of this study was to compare metastatic capabilities of malignant tumor cells after irradiation with photon, proton, and carbon ion beams to clarify their ion beam–specific biological effects. We examined the biological properties of highly aggressive HT1080 human fibrosarcoma cells to assess their metastatic processes in terms of cell adhesion capability to extracellular matrix, expression of integrins, cell migration, cell invasive capability, and matrix metalloproteinase-2 activity in vitro. We then assessed the metastatic capabilities of LM8 mouse osteosarcoma irradiated with carbon ion or photon beam in the syngeneic mice. Both proton and carbon ion irradiation decreased cell migration and invasion in a dose-dependent manner and strongly inhibited matrix metalloproteinase-2 activity. On the other hand, lower X-ray irradiation promoted cell migration and invasion concomitant with up-regulation of Vß3 integrin. For cancer cells treated with carbon ion irradiation, the number of pulmonary metastasis was decreased significantly in vivo. These findings suggest that particle irradiation suppresses metastatic potential even at lower dose, whereas photon irradiation promotes cell migration and invasive capabilities at lower dose level, and provide preclinical evidence that ion beam radiotherapy may be superior to conventional photon beam therapy in possible preventive effects on metastases of irradiated malignant tumor cells.

Key Words: proton • carbon ion • X-ray • integrin • MMP

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