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ID 51440
フルテキストURL
著者
Obika, Masanari Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Ogawa, Hiroko Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Takahashi, Katsuyuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Li, Jiayi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Hatipoglu, Omer Faruk Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Cilek, Mehmet Zeynel Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Miyoshi, Toru Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Inagaki, Junko Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Ohtsuki, Takashi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Kusachi, Shozo Okayama Univ, Grad Sch Hlth Sci, Dept Med Technol
Ninomiya, Yoshifumi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
Hirohata, Satoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem
抄録
Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z-vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor-bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity.
発行日
2012-10
出版物タイトル
Cancer Science
103巻
10号
出版者
Wiley-Blackwell
開始ページ
1889
終了ページ
1897
ISSN
1347-9032
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1111/j.1349-7006.2012.02381.x
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/51444
言語
English
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT