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CD93 promotes beta(1) integrin activation and fibronectin fibrillogenesis during tumor angiogenesis
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centre for Research and Development, Uppsala University, Gävle Hospital, Gävle, Sweden.ORCID iD: 0000-0003-1351-5153
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2018 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 128, no 8, p. 3280-3297Article in journal (Refereed) Published
Abstract [en]

Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is upregulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates beta(1) integrin signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytic cleavage. The CD93-MMRN2 complex was required for activation of beta(1) integrin, phosphorylation of focal adhesion kinase (FAK), and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of beta(1) integrin and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for therapy.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC , 2018. Vol. 128, no 8, p. 3280-3297
National Category
Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-151062DOI: 10.1172/JCI97459ISI: 000440461500015PubMedID: 29763414Scopus ID: 2-s2.0-85051280272OAI: oai:DiVA.org:umu-151062DiVA, id: diva2:1245141
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-09-04Bibliographically approved

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Bergqvist, Michael

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