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EphB4 mediates resistance to antiangiogenic therapy in experimental glioma

Christian Uhl1, Moritz Markel1, Thomas Broggini1

  • 1Department of Neurosurgery, Universitätsmedizin Charite - Campus Mitte, Luisenstrasse 46, 10117, Berlin, Germany.

Angiogenesis
|July 11, 2018
PubMed
Abstract

Insights

EphB4 overexpression promotes antiangiogenesis resistance in SF126 glioma models by altering tumor vascular morphogenesis and pericyte coverage. This leads to larger, treatment-resistant vessels and impacts cellular proliferation and apoptosis.

Area of Science:

  • Oncology
  • Vascular Biology
  • Molecular Biology

Background:

  • Tumor vascular morphogenesis is crucial for antiangiogenesis therapy resistance.
  • The ephrinB2-EphB4 system plays a role in regulating vascular morphogenesis.
  • Understanding EphB4's influence is key to overcoming treatment resistance in glioma.

Purpose of the Study:

  • To investigate the impact of EphB4 overexpression on tumor microcirculation.
  • To characterize the resistance mechanisms in SF126 glioma models after antiangiogenic treatment.

Main Methods:

  • SF126 glioma cells were co-implanted with EphB4-overexpressing or control cells.
  • Tumor growth was monitored using MRI.
  • Microcirculation was analyzed via intravital microscopy before and after Sunitinib treatment.
  • Immunohistochemistry assessed cell proliferation and apoptosis.

Main Results:

  • EphB4 overexpression resulted in larger, treatment-resistant tumor vessels.
  • Pericyte-endothelial cell interactions were maintained under EphB4 overexpression.
  • Reduced antiproliferative and proapoptotic responses were observed with EphB4 overexpression.

Conclusions:

  • EphB4 overexpression contributes to vascular resistance in experimental glioma models.
  • Altered vascular morphogenesis, pericyte coverage, and cellular responses mediate this resistance.
Keywords:
Antiangiogenic therapyEphB4EphrinGlioblastoma multiformeIntravital microscopyPericyte

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