Abstract

Abstract Angiogenesis plays critical roles during development and progression of cancer. Members of the bone morphogenetic protein (BMP) family are involved in TGF-beta superfamily, and have been implicated in the development and maintenance of vascular systems. While BMP-9 and 10 have been recently reported to bind to ALK-1 in endothelial cells, the roles of BMP-9/ALK-1 signaling in the regulation of endothelial cells have not yet been fully elucidated. Here, we examined the effects of BMP-9 on the proliferation of endothelial cells using various systems. Vascular tube formation from ex vivo allantoic explants of mouse embryos was promoted by BMP-9. BMP-9 also induced the proliferation of in vitro-cultured mouse embryonic stem cell-derived endothelial cells (MESEC) by inducing the expression of vascular endothelial growth factor receptor 2 and Tie2, a receptor for Angiopoietin-1. Decrease in ALK-1 expression and expression of constitutively active ALK-1 in MESEC abrogated and mimicked the effects of BMP-9 on the proliferation of MESEC, respectively, suggesting that BMP-9 promotes their proliferation via ALK-1. Furthermore, in vivo angiogenesis was promoted by BMP-9 in a Matrigel plug assay and a BxPC3 human pancreatic cancer xenograft model. In consistent with these in vivo findings, BMP-9 enhanced the proliferation of in vitro cultured normal endothelial cells from dermal tissues of adult mice and tumor-associated endothelial cells isolated from tumor xenografts in host mice. These findings suggest that BMP-9 signaling activates the endothelium via ALK-1. In this presentation, the roles of BMP-9 signals in the formation of lymphatic vessels will also be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5276. doi:1538-7445.AM2012-5276

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