Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with alpha 2 integrin
2015 (English)In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 48, 89-99 p.Article in journal (Refereed) Published
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 α-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 α2 integrin, the major collagen-binding α-integrin subunit in ECs, showed increased binding of HRG compared with wild type C2C12 cells lacking the α2 subunit. Recombinant α2 I-domain protein bound HRG and to a higher extent when in active conformation. However, the α2 I-domain bound weakly to HRG compared with COL I and the purified α2β1 ectodomain complex failed to retain HRG. We conclude that HRG binds to α2 integrin through low-affinity interactions in a HS-independent manner, thereby blocking EC-adhesion to COL I.
Place, publisher, year, edition, pages
2015. Vol. 48, 89-99 p.
HRG; Adhesion; Integrin; Endothelial cells; Collagen
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-273699DOI: 10.1016/j.matbio.2015.06.002ISI: 000366617000009PubMedID: 26051322OAI: oai:DiVA.org:uu-273699DiVA: diva2:894941
FunderSwedish Research CouncilSwedish Cancer SocietyKnut and Alice Wallenberg Foundation