Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival

Cancer Res. 2015 Nov 1;75(21):4504-16. doi: 10.1158/0008-5472.CAN-14-3636. Epub 2015 Sep 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / pathology
  • Animals
  • Antigens, CD / genetics
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cadherins / genetics
  • Capillary Permeability / genetics
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism*
  • Glioblastoma / blood supply*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Pathologic / genetics*
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Complement / genetics
  • Receptors, Complement / metabolism*
  • Stress Fibers / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Antigens, CD
  • Cadherins
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • Receptors, Complement
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • cadherin 5
  • complement 1q receptor