| First Author | Murphy PA | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 3 | Pages | e0120872 |
| PubMed ID | 25807551 | Mgi Jnum | J:229618 |
| Mgi Id | MGI:5752691 | Doi | 10.1371/journal.pone.0120872 |
| Citation | Murphy PA, et al. (2015) Tumor angiogenesis in the absence of fibronectin or its cognate integrin receptors. PLoS One 10(3):e0120872 |
| abstractText | Binding of alpha5beta1 and alphavbeta3/beta5 integrin receptors on the endothelium to their fibronectin substrate in the extracellular matrix has been targeted as a possible means of blocking tumor angiogenesis and tumor growth. However, clinical trials of blocking antibodies and peptides have been disappointing despite promising preclinical results, leading to questions about the mechanism of the inhibitors and the reasons for their failure. Here, using tissue-specific and inducible genetics to delete the alpha5 and alphav receptors in the endothelium or their fibronectin substrate, either in the endothelium or globally, we show that both are dispensable for tumor growth, in transplanted tumors as well as spontaneous and angiogenesis-dependent RIP-Tag-driven pancreatic adenocarcinomas. In the nearly complete absence of fibronectin, no differences in vascular density or the deposition of basement membrane laminins, ColIV, Nid1, Nid2, or the TGFbeta binding matrix proteins, fibrillin-1 and -2, could be observed. Our results reveal that fibronectin and the endothelial fibronectin receptor subunits, alpha5 and alphav, are dispensable for tumor angiogenesis, suggesting that the inhibition of angiogenesis induced by antibodies or small molecules may occur through a dominant negative effect, rather than a simple functional block. |
