Heavy ion irradiation inhibits in vitro angiogenesis even at sublethal dose

Yutaka Takahashi, Teruki Teshima, Naomasa Kawaguchi, Yoshinosuke Hamada, Seiji Mori, Ayako Madachi, Satoko Ikeda, Hirokazu Mizuno, Toshiyuki Ogata, Kumie Nojima, Yoshiya Furusawa, Nariaki Matsuura

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Angiogenesis is essential for tumor growth and metastasis. Because endothelial cells are genetically stable, they rarely acquire resistance to anticancer modalities, and could, thus, be a suitable target for radiation therapy. Heavy ion radiation therapy has attracted attention as an effective modality for cancer therapy because of its highly lethal effects, but the effects of heavy ion irradiation on in vitro cell function associated with angiogenesis have not been reported. Our study found that in vitro angiogenesis was inhibited by high linear energy transfer carbon ion irradiation even at sublethal dose (0.1 Gy). ECV304 and HUVEC human umbilical vascular endothelial cells were irradiated with 290 MeV carbon ion beams of approximately 110 keV/μm or 4 MV X-ray of approximately 1 keV/μm. Their adhesiveness and migration to vitronectin or osteopontin were inhibited, and capillary-like tube structures in three-dimensional culture were destroyed after carbon ion irradiation concomitant with the inhibition of matrix metalloproteinase-2 activity, down-regulation of αVβ3 integrin, which is one of the adhesion molecules, slight up-regulation of membrane type1- matrix metalloproteinase, and significant up-regulation of tissue inhibitor of metalloproteinase-2. On the other hand, sublethal X-ray irradiation promoted migration of endothelial cells, and the capillary-like tube structure in three-dimensional culture progressed even after 16 Gy irradiation. These results provide an implication that heavy ion beam therapy could be superior to conventional photon beam therapy in preventive effects on in vitro angiogenesis even at sublethal dose, and might inhibit angiogenesis in vivo.

Original languageEnglish (US)
Pages (from-to)4253-4257
Number of pages5
JournalCancer Research
Issue number14
StatePublished - Jul 15 2003


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