| First Author | Roche F | Year | 2015 |
| Journal | Matrix Biol | Volume | 48 |
| Pages | 89-99 | PubMed ID | 26051322 |
| Mgi Jnum | J:229434 | Mgi Id | MGI:5751964 |
| Doi | 10.1016/j.matbio.2015.06.002 | Citation | Roche F, et al. (2015) Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with alpha2 integrin. Matrix Biol 48:89-99 |
| abstractText | The plasma protein histidine-rich glycoprotein (HRG) affects the morphology and function of both endothelial cells (ECs) and monocytes/macrophages in cancer. Here, we examined the mechanism of action of HRG's effect on ECs. HRG suppressed adhesion, spreading and migration of ECs specifically on collagen I (COL I) whereas ECs seeded on other extracellular matrix proteins were insensitive to HRG. HRG did not bind specifically to COL I or to the alpha-integrin binding site on collagen, GFOGER. Furthermore, HRG's inhibition of EC adhesion was not dependent upon heparan sulfate (HS) moieties as heparitinase-treated ECs remained sensitive to HRG. C2C12 cells expressing alpha2 integrin, the major collagen-binding alpha-integrin subunit in ECs, showed increased binding of HRG compared with wild type C2C12 cells lacking the alpha2 subunit. Recombinant alpha2 I-domain protein bound HRG and to a higher extent when in active conformation. However, the alpha2 I-domain bound weakly to HRG compared with COL I and the purified alpha2beta1 ectodomain complex failed to retain HRG. We conclude that HRG binds to alpha2 integrin through low-affinity interactions in a HS-independent manner, thereby blocking EC-adhesion to COL I. |
