Dual role of pericyte α6β1-integrin in tumour blood vessels.

Fiche publication

Date publication

mars 2017

Journal

Journal of cell science

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DE ARCANGELIS Adèle

Tous les auteurs :
Reynolds LE, D'Amico G, Lechertier T, Papachristodoulou A, Muñoz-Félix JM, De Arcangelis A, Baker M, Serrels B, Hodivala-Dilke KM

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/28289267

Résumé

The integrin α6β1 is a major laminin receptor, and formation of a laminin-rich basement membrane is a key feature in tumour blood vessel stabilisation and pericyte recruitment; processes that are important in the growth and maturation of tumour blood vessels. However, the role of pericyte α6β1-integrin in angiogenesis is largely unknown. We developed mice where the α6-integrin subunit is deleted in pericytes and examined tumour angiogenesis and growth. These mice had: i) reduced pericyte coverage of tumour blood vessels; ii) reduced tumour blood vessel stability; iii) increased blood vessel diameter; iv) enhanced leakiness and, v) abnormal blood vessel basement membrane architecture. Surprisingly, tumour growth, blood vessel density and metastasis were not altered. Analysis of retinas revealed that deletion of pericyte α6-integrin did not affect physiological angiogenesis. At the molecular level, we provide evidence that pericyte α6-integrin controls PDGFRβ expression and AKT/mTOR signalling. Together, we show that pericyte α6β1-integrin regulates tumour blood vessels by both controlling PDGFRβ and basement membrane architecture. These data establish a novel dual role for pericyte α6-integrin that affects the blood vessel phenotype during pathological angiogenesis.