Author: ["Giorgio Seano","Giulia Chiaverina","Paolo Armando Gagliardi","Laura di Blasio","Alberto Puliafito","Claire Bouvard","Roberto Sessa","Guido Tarone","Lydia Sorokin","Dominique Helley","Rakesh K. Jain","Guido Serini","Federico Bussolino","Luca Primo"]
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Abstract
The mechanism by which angiogenic endothelial cells break the physical barrier of the vascular basement membrane and consequently sprout to form new vessels in mature tissues is unclear. Here, we show that the angiogenic endothelium is characterized by the presence of functional podosome rosettes. These extracellular-matrix-degrading and adhesive structures are precursors of de novo branching points and represent a key feature in the formation of new blood vessels. VEGF-A stimulation induces the formation of endothelial podosome rosettes by upregulating integrin α6β1. In contrast, the binding of α6β1 integrin to the laminin of the vascular basement membrane impairs the formation of podosome rosettes by restricting α6β1 integrin to focal adhesions and hampering its translocation to podosomes. Using an ex vivo sprouting angiogenesis assay, transgenic and knockout mouse models and human tumour sample analysis, we provide evidence that endothelial podosome rosettes control blood vessel branching and are critical regulators of pathological angiogenesis. Seano, Primo and colleagues report that blood vessel branching during tumour angiogenesis is mediated by the formation of podosome rosettes that depends on VEGF-A and integrin α6β1.Cite this article
Seano, G., Chiaverina, G., Gagliardi, P. et al. Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis. Nat Cell Biol 16, 931–941 (2014). https://doi.org/10.1038/ncb3036 