VEGFR-3 sprouts out

Finnish researchers have found a new role for VEGFR-3 in angiogenic 'sprouts' and report that blocking molecular signalling with monoclonal antibodies inhibited angiogenesis and tumour growth.

The researchers, led by Professor Kari Alitalo from the Ludwig Institute for Cancer Research at the University of Helsinki, found that the tyrosine kinase VEGFR-3 (vascular endothelial growth factor receptor 3), is highly expressed in angiogenic sprouts, in which endothelial cells proliferate and connect to neighbouring blood vessels, eventually forming new ones.

The researchers report their findings today on Nature's website.

The receptor VEGFR-2 is already known to be important for angiogenesis and is a target for drug development globally. The researchers found that stimulation of VEGFR-3 augmented and sustained angiogenesis, even in the presence of VEGFR-2 inhibitors.

Antibodies against both receptors in combination resulted in even more inhibition of angiogenesis and tumour growth.

They also found that disruption of the Notch signalling pathway - important for cell-cell communication but dysregulated in many cancers - led to widespread endothelial VEGFR-3 expression and excessive sprouting.

The researchers write that their findings implicate the receptor as a regulator of vascular network formation and that targeting it may provide additional efficacy for anti-angiogenic therapies.