Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme

Yu Qin, Masamichi Takahashi, Kristopher Sheets, Horacio Soto, Jessica Tsui, Panayiotis Pelargos, Joseph P. Antonios, Noriyuki Kasahara, Isaac Yang, Robert M. Prins, Jonathan Braun, Lynn K. Gordon, Madhuri Wadehra

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.

Original languageEnglish (US)
Pages (from-to)29-40
Number of pages12
JournalJournal of neuro-oncology
Volume134
Issue number1
DOIs
StatePublished - Aug 1 2017

Keywords

  • Angiogenesis
  • EMP2
  • GBM
  • Immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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    Qin, Y., Takahashi, M., Sheets, K., Soto, H., Tsui, J., Pelargos, P., Antonios, J. P., Kasahara, N., Yang, I., Prins, R. M., Braun, J., Gordon, L. K., & Wadehra, M. (2017). Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme. Journal of neuro-oncology, 134(1), 29-40. https://doi.org/10.1007/s11060-017-2507-8