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CD93 promotes integrin-β1 activation and fibronectin fibrillogenesis during tumor angiogenesis.
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2018 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, article id 97459Article in journal (Refereed) Epub ahead of print
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 up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-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 proteolytical cleavage. The CD93-MMRN2 complex was required for activation of integrin-β1, 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 integrin-β1 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
2018. article id 97459
Keyword [en]
Brain cancer, Fibronectin, Oncology, Vascular Biology, endothelial cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-350902DOI: 10.1172/JCI97459PubMedID: 29763414OAI: oai:DiVA.org:uu-350902DiVA, id: diva2:1206494
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-05-17

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