Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer

H. Kaneda, T. Arao, K. Matsumoto, M. A. De Velasco, D. Tamura, K. Aomatsu, K. Kudo, K. Sakai, T. Nagai, Y. Fujita, K. Tanaka, K. Yanagihara, Y. Yamada, I. Okamoto, K. Nakagawa, K. Nishio

研究成果: Contribution to journalArticle査読

55 被引用数 (Scopus)

抄録

Background: Activin A is a multi-functional cytokine belonging to the transforming growth factor-Β (TGF-Β) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin Β A subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC. Methods: Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a stable INHBA-introduced GC cell line in vivo. Results: Compared with TGF-Β, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis in vivo. Conclusion: Our findings highlight the suppressive role of activin A, unlike TGF-Β, on tumour growth and angiogenesis in GC.

本文言語英語
ページ(範囲)1210-1217
ページ数8
ジャーナルBritish journal of cancer
105
8
DOI
出版ステータス出版済み - 10 11 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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