Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis

被引：96

作者：

Seano, Giorgio ^{[1
,2
,3
]}

Chiaverina, Giulia ^{[1
,2
]}

Gagliardi, Paolo Armando ^{[1
,2
]}

di Blasio, Laura ^{[1
,2
]}

Puliafito, Alberto ^{[1
,2
]}

Bouvard, Claire ^{[4
]}

Sessa, Roberto ^{[1
,2
]}

Tarone, Guido ^{[5
]}

Sorokin, Lydia ^{[6
]}

Helley, Dominique ^{[7
]}

Jain, Rakesh K. ^{[3
]}

Serini, Guido ^{[1
,2
]}

Bussolino, Federico ^{[1
,2
]}

Primo, Luca ^{[1
,2
]}

机构：

[1] Univ Turin, Dept Oncol, I-10100 Turin, Italy

[2] IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy

[3] Harvard Univ, Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Sch Med, Boston, MA 02114 USA

[4] Univ Paris 05, UMR S 765, Sorbonne Paris Cite, F-75006 Paris, France

[5] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, I-10124 Turin, Italy

[6] Univ Munster, Inst Physiol Chem & Pathobiochem, D-48149 Munster, Germany

[7] Univ Paris 05, UMR S 970, Sorbonne Paris Cite, F-75006 Paris, France

来源：

NATURE CELL BIOLOGY | 2014年 / 16卷 / 10期

关键词：

GROWTH-FACTOR; EXTRACELLULAR-MATRIX; CELLS; INTEGRIN; MEMBRANE; INVADOPODIA; EXPRESSION; CANCER; MICE; METASTASIS;

D O I：

10.1038/ncb3036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 alpha(6)beta(1). In contrast, the binding of alpha(6)beta(1) integrin to the laminin of the vascular basement membrane impairs the formation of podosome rosettes by restricting alpha(6)beta(1) 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.

引用

页码：931 / 941

页数：11

共 45 条

[1] Podosome-type adhesions and focal adhesions, so alike yet so different [J].