title: Particle irradiation suppresses metastatic potential of cancer cells.
abstract: 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 alphaVbeta3 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.
authors.affiliation: Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ogata
authors.forename: Teruki
authors.initials: T
authors.lastname: Teshima
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kagawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hishikawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Suzumoto
authors.forename: Kumie
authors.initials: K
authors.lastname: Nojima
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D002448:Cell Adhesion / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005109:Extracellular Matrix / Q000528:radiation effects; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D016023:Integrins / Q000528:radiation effects; D007700:Kinetics; D009362:Neoplasm Metastasis / Q000517:prevention & control / Q000532:radiotherapy*; D010315:Particle Accelerators; D017785:Photons; D011522:Protons
chemical_list: D016023:Integrins; D011522:Protons