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Dual role of pericyte α6β1-integrin in tumour blood vessels.
- Source :
-
Journal of cell science [J Cell Sci] 2017 May 01; Vol. 130 (9), pp. 1583-1595. Date of Electronic Publication: 2017 Mar 13. - Publication Year :
- 2017
-
Abstract
- The α6β1-integrin 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: (1) reduced pericyte coverage of tumour blood vessels; (2) reduced tumour blood vessel stability; (3) increased blood vessel diameter; (4) enhanced blood vessel leakiness, and (5) 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. Taken 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 as modulating the blood vessel phenotype during pathological angiogenesis.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Basement Membrane drug effects
Basement Membrane metabolism
Becaplermin
Blood Vessels drug effects
Blood Vessels pathology
Cell Line, Tumor
Cell Proliferation drug effects
Integrases metabolism
Mice
Neoplasm Metastasis
Neoplasms metabolism
Neoplasms pathology
Pericytes drug effects
Proto-Oncogene Proteins c-sis pharmacology
Receptor, Platelet-Derived Growth Factor beta metabolism
Blood Vessels metabolism
Integrin alpha6beta1 metabolism
Neoplasms blood supply
Pericytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 130
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 28289267
- Full Text :
- https://doi.org/10.1242/jcs.197848