EphrinB2–EphB4 Signaling in Neurooncological Disease |
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Authors: | Andras Piffko Christian Uhl Peter Vajkoczy Marcus Czabanka Thomas Broggini |
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Affiliation: | 1.Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany;2.Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA;3.Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA;4.Department of Neurosurgery, University Medicine Charité, 10117 Berlin, Germany; (C.U.); (P.V.);5.Department of Neurosurgery, University Hospital Frankfurt, 60528 Frankfurt am Main, Germany; |
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Abstract: | EphrinB2–EphB4 signaling is critical during embryogenesis for cardiovascular formation and neuronal guidance. Intriguingly, critical expression patterns have been discovered in cancer pathologies over the last two decades. Multiple connections to tumor migration, growth, angiogenesis, apoptosis, and metastasis have been identified in vitro and in vivo. However, the molecular signaling pathways are manifold and signaling of the EphB4 receptor or the ephrinB2 ligand is cancer type specific. Here we explore the impact of these signaling pathways in neurooncological disease, including glioma, brain metastasis, and spinal bone metastasis. We identify potential downstream pathways that mediate cancer suppression or progression and seek to understand it´s role in antiangiogenic therapy resistance in glioma. Despite the Janus-faced functions of ephrinB2–EphB4 signaling in cancer Eph signaling remains a promising clinical target. |
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Keywords: | EphB4 ephrinB2 metastasis glioblastoma glioma bone brain metastasis spinal metastasis neurooncology bone metastasis |
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