| First Author | Reynolds LE | Year | 2017 |
| Journal | J Cell Sci | Volume | 130 |
| Issue | 9 | Pages | 1583-1595 |
| PubMed ID | 28289267 | Mgi Jnum | J:249588 |
| Mgi Id | MGI:5922490 | Doi | 10.1242/jcs.197848 |
| Citation | Reynolds LE, et al. (2017) Dual role of pericyte alpha6beta1-integrin in tumour blood vessels. J Cell Sci 130(9):1583-1595 |
| abstractText | The alpha6beta1-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 alpha6beta1-integrin in angiogenesis is largely unknown. We developed mice where the alpha6-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 alpha6-integrin did not affect physiological angiogenesis. At the molecular level, we provide evidence that pericyte alpha6-integrin controls PDGFRbeta expression and AKT-mTOR signalling. Taken together, we show that pericyte alpha6beta1-integrin regulates tumour blood vessels by both controlling PDGFRbeta and basement membrane architecture. These data establish a novel dual role for pericyte alpha6-integrin as modulating the blood vessel phenotype during pathological angiogenesis. |
