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Elevated Expression of the C-Type Lectin CD93 in the Glioblastoma Vasculature Regulates Cytoskeletal Rearrangements That Enhance Vessel Function and Reduce Host Survival
Uppsala University, Science for Life Laboratory, SciLifeLab. 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 Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. 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 Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2015 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no 21, 4504-4516 p.Article in journal (Refereed) Published
Abstract [en]

Glioblastoma is an aggressive brain tumor characterized by an abnormal blood vasculature that is hyperpermeable. Here, we report a novel role for CD93 in regulating angiogenesis in this setting by modulating cell-cell and cell-matrix adhesion of endothelial cells. Tissue microarray analysis demonstrated that vascular expression of CD93 was correlated with poor survival in a clinical cohort of patients with high-grade astrocytic glioma. Similarly, intracranial growth in the GL261 mouse model of glioma was delayed significantly in CD93(-/-) hosts, resulting in improved survival compared with wild-type mice. This effect was associated with increased vascular permeability and decreased vascular perfusion of tumors, indicating reduced vessel functionality in the absence of CD93. RNAi-mediated attenuation of CD93 in endothelial cells diminished VEGF-induced tube formation in a three-dimensional collagen gel. CD93 was required for efficient endothelial cell migration and proper cell polarization in vitro. Further, in endothelial cells where CD93 was attenuated, decreased cell spreading led to a severe reduction in cell adhesion, a lack of proper cell contacts, a loss of VE-cadherin, and aberrant actin stress fiber formation. Our results identify CD93 as a key regulator of glioma angiogenesis and vascular function, acting via cytoskeletal rearrangements required for cell-cell and cell-matrix adhesion.

Place, publisher, year, edition, pages
2015. Vol. 75, no 21, 4504-4516 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-269008DOI: 10.1158/0008-5472.CAN-14-3636ISI: 000365602200009PubMedID: 26363010OAI: oai:DiVA.org:uu-269008DiVA: diva2:881945
Funder
Swedish Cancer Society, CAN 2011/862Swedish Childhood Cancer Foundation, PR2013-0107, PROJ11/083Swedish Research Council, 2013-3797, 2008-2853
Available from: 2015-12-11 Created: 2015-12-11 Last updated: 2017-12-01Bibliographically approved

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Zhang, LeiLugano, RobertaHuang, HuaElhassan, Tamador Elsir AbuGeorganaki, MariaEssand, MagnusPontén, FredrikSmits, AnjaDimberg, Anna

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Zhang, LeiLugano, RobertaHuang, HuaElhassan, Tamador Elsir AbuGeorganaki, MariaEssand, MagnusPontén, FredrikSmits, AnjaDimberg, Anna
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Science for Life Laboratory, SciLifeLabDepartment of Immunology, Genetics and PathologyNeurologyClinical ImmunologyVascular Biology
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