Format

Send to

Choose Destination
Nat Cell Biol. 2014 Oct;16(10):931-41, 1-8. doi: 10.1038/ncb3036. Epub 2014 Sep 14.

Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis.

Author information

1
1] Department of Oncology, University of Torino, Turin 10100, Italy [2] Candiolo Cancer Institute-FPO, IRCCS, Candiolo 10060, Italy [3] Edwin L. Steele Laboratory for Tumor Biology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
2
1] Department of Oncology, University of Torino, Turin 10100, Italy [2] Candiolo Cancer Institute-FPO, IRCCS, Candiolo 10060, Italy.
3
UMR-S 765, Université Paris Descartes, Sorbonne Paris Cité, Paris 75006, France.
4
Department of Molecular Biotechnology and Health Sciences, University of Torino, Molecular Biotechnology Center, Turin 10124, Italy.
5
Institute of Physiological Chemistry and Pathobiochemistry, Muenster University, Muenster 48149, Germany.
6
UMR-S 970, Université Paris Descartes, Sorbonne Paris Cité, Paris 75006, France.
7
Edwin L. Steele Laboratory for Tumor Biology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

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.

PMID:
25218639
PMCID:
PMC4564017
DOI:
10.1038/ncb3036
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center