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Elevated Expression...
Elevated Expression of the C-Type Lectin CD93 in the Glioblastoma Vasculature Regulates Cytoskeletal Rearrangements That Enhance Vessel Function and Reduce Host Survival
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- Langenkamp, Elise (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Zhang, Lei (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Lugano, Roberta (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Huang, Hua (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Elhassan, Tamador Elsir Abu (author)
- Karolinska Institutet,Uppsala universitet,Neurologi
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- Georganaki, Maria (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Bazzar, Wesam (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Lööf, Johan (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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Trendelenburg, George (author)
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- Essand, Magnus (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Pontén, Fredrik (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Smits, Anja (author)
- Uppsala universitet,Neurologi
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- Dimberg, Anna (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2015
- 2015
- English.
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 75:21, s. 4504-4516
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Langenkamp, Elis ...
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Zhang, Lei
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Lugano, Roberta
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Huang, Hua
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Elhassan, Tamado ...
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Georganaki, Mari ...
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show more...
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Bazzar, Wesam
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Lööf, Johan
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Trendelenburg, G ...
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Essand, Magnus
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Pontén, Fredrik
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Smits, Anja
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Dimberg, Anna
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Uppsala University
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Karolinska Institutet