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

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Abstract

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.

Original languageEnglish
Pages (from-to)1210-1217
Number of pages8
JournalBritish journal of cancer
Volume105
Issue number8
DOIs
Publication statusPublished - Oct 11 2011
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kaneda, H., Arao, T., Matsumoto, K., De Velasco, M. A., Tamura, D., Aomatsu, K., ... Nishio, K. (2011). Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer. British journal of cancer, 105(8), 1210-1217. https://doi.org/10.1038/bjc.2011.348