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Oncotarget. 2015 Mar 30;6(9):7293-304.

Plexin-B2 promotes invasive growth of malignant glioma.

Author information

1
Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Translational Neuro-Oncology Laboratories, Moores UCSD Cancer Center and Department of Neurosciences, La Jolla, CA, USA.
3
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Comprehensive Brain Tumor Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

Invasive growth is a major determinant of the high lethality of malignant gliomas. Plexin-B2, an axon guidance receptor important for mediating neural progenitor cell migration during development, is upregulated in gliomas, but its function therein remains poorly understood. Combining bioinformatic analyses, immunoblotting and immunohistochemistry of patient samples, we demonstrate that Plexin-B2 is consistently upregulated in all types of human gliomas and that its expression levels correlate with glioma grade and poor survival. Activation of Plexin-B2 by Sema4C ligand in glioblastoma cells induced actin-based cytoskeletal dynamics and invasive migration in vitro. This proinvasive effect was associated with activation of the cell motility mediators RhoA and Rac1. Furthermore, costimulation of Plexin-B2 and the receptor tyrosine kinase Met led to synergistic Met phosphorylation. In intracranial glioblastoma transplants, Plexin-B2 knockdown hindered invasive growth and perivascular spreading, and resulted in decreased tumor vascularity. Our results demonstrate that Plexin-B2 promotes glioma invasion and vascularization, and they identify Plexin-B2 as a potential novel prognostic marker for glioma malignancy. Targeting the Plexin-B2 pathway may represent a novel therapeutic approach to curtail invasive growth of glioblastoma.

KEYWORDS:

glioma invasion; plexin; semaphorin; tumor vasculature

PMID:
25762646
PMCID:
PMC4466685
DOI:
10.18632/oncotarget.3421
[Indexed for MEDLINE]
Free PMC Article

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