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Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with alpha 2 integrin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Staffan Johansson)
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2015 (English)In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 48, 89-99 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
HRG; Adhesion; Integrin; Endothelial cells; Collagen
National Category
Cell and Molecular Biology
URN: urn:nbn:se:uu:diva-273699DOI: 10.1016/j.matbio.2015.06.002ISI: 000366617000009PubMedID: 26051322OAI: oai:DiVA.org:uu-273699DiVA: diva2:894941
Swedish Research CouncilSwedish Cancer SocietyKnut and Alice Wallenberg Foundation
Available from: 2016-01-17 Created: 2016-01-17 Last updated: 2016-01-21Bibliographically approved

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Roche, FrancisStaffan, JohanssonClaesson-Welsh, Lena
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Department of Immunology, Genetics and PathologyDepartment of Medical Biochemistry and MicrobiologyVascular Biology
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