Role of BMPs in tumor angiogenesis

Angiogenesis

Scheme of tumor-induced angiogenesis (adapted from Carmeliet & Jain, Nature, 2011) and sprouting angiogenesis from a HUVEC spheroid (work by A. Benn, Knaus Lab)

Sprouting angiogenesis describes the formation of new blood vessels from pre-existing vasculature, a mechanism essential during embryonic development, but also in tumor-induced angiogenesis.

In the past, in vivo targeting of BMP pathway proteins gave rise to multiple vascular phenotypes uncovering BMP signaling to be essential for angiogenic processes by acting on cells that constitute blood vessels, such as endothelial cells and smooth muscle cells. Interestingly, recent research suggests BMPs to regulate endothelial cell function and induce sprouting angiogenesis independent of VEGF signals. However, a detailed molecular understanding of BMP signal transduction in the vascular system, termed ‘vascular BMP signaling’, is still missing and the individual contribution of the BMP-induced signaling pathways in this process is barely understood.

To address these questions we perform in vitro angiogenesis assays, as well as ex vivo organ culture models to characterize vascular BMP signaling. In particular, we are interested in elucidating the role of BMPs on sprouting angiogenesis and identify novel key effectors. We aim to gain a more accurate molecular understanding of vascular BMP signal transduction, the role of individual BMP receptors and related key signal transduction proteins. This detailed molecular knowledge is essential to the development of novel anti-angiogenic therapies but also to gain a better view on how BMPs orchestrate angiogenesis.