Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis

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

Research output: Contribution to journalArticle

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 α6 β1. 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.

Original languageEnglish
Pages (from-to)931-941
Number of pages11
JournalNature Cell Biology
Volume16
Issue number10
DOIs
Publication statusPublished - Jan 1 2014

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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