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

作者：Kaneda H; Arao T; Matsumoto K; De Velasco M A; Tamura D; Aomatsu K; Kudo K; Sakai K; Nagai T; Fujita Y; Tanaka K; Yanagihara K; Yamada Y; Okamoto I; Nakagawa K; Nishio K^*

来源：British Journal of Cancer, 2011, 105(8): 1210-1217.

DOI：10.1038/bjc.2011.348

• activin A
• p21(CIP1/WAF1)
• angiogenesis
• gastric cancer

BACKGROUND: Activin A is a multi-functional cytokine belonging to the transforming growth factor-beta (TGF-beta) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin beta 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-beta, 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-beta, on tumour growth and angiogenesis in GC. British Journal of Cancer (2011) 105, 1210-1217. doi:10.1038/bjc.2011.348 www.bjcancer.

• 出版日期2011-10-11