ELTD1, an effective anti-angiogenic target for gliomas: Preclinical assessment in mouse GL261 and human G55 xenograft glioma models

Jadith Ziegler, Richard Pody, Patricia Coutinho De Souza, Blake Evans, Debra Saunders, Nataliya Smith, Samantha Mallory, Charity Njoku, Yunzhou Dong, Hong Chen, Jiali Dong, Megan Lerner, Osamah Mian, Sai Tummala, James Battiste, Kar Ming Fung, Jonathan D. Wren, Rheal A. Towner

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Despite current therapies, glioblastoma is a devastating cancer, and validation of effective biomarkers for it will enable better diagnosis and therapeutic intervention for this disease. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domaincontaining protein 1 on chromosome 1) via bioinformatics, and validated that ELTD1 protein levels are significantly higher in human and rodent gliomas. The focus of this study was to assess the effect on tumor growth of an antibody against ELTD1 in orthotopic, GL261, and G55 xenograft glioma models. Methods: The effect of anti-ELTD1 antibody therapy was assessed by animal survival, MRI measured tumor volumes, MR angiography, MR perfusion imaging, and immunohistochemistry (IHC) characterization of microvessel density in mouse glioma models. Comparative treatments included anti-vascular endothelial growth factor (VEGF) and anti-c-Met antibody therapies, compared with untreated controls. Results: Tumor volume and survival data in this study show that antibodies against ELTD1 inhibit glioma growth just as effectively or even more so compared with other therapeutic targets studied, including anti-VEGF antibody therapy. Untreated GL261 or G55 tumors were found to have significantly higher ELTD1 levels (IHC) compared with contralateral normal brain. The anti-angiogenic effect of ELTD1 antibody therapy was observed in assessment of microvessel density, as well as from MR angiography and perfusion measurements, which indicated that anti-ELTD1 antibody therapy significantly decreased vascularization compared with untreated controls. Conclusions: Either as a single therapy or in conjunction with other therapeutic approaches, anti-ELTD1 antibodies could be a valuable new clinical anti-angiogenic therapeutic for high-grade gliomas.

Original languageEnglish (US)
Pages (from-to)175-185
Number of pages11
JournalNeuro-oncology
Volume19
Issue number2
DOIs
StatePublished - Jan 1 2017

Keywords

  • Anti-ELTD1 antibody
  • ELTD1 ([Epidermal Growth Factor (EGF)
  • Gl261 and G55 gliomas
  • Latrophilin and seven transmembrane domain-containing 1] on chromosome 1)
  • MRI

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Ziegler, J., Pody, R., De Souza, P. C., Evans, B., Saunders, D., Smith, N., Mallory, S., Njoku, C., Dong, Y., Chen, H., Dong, J., Lerner, M., Mian, O., Tummala, S., Battiste, J., Fung, K. M., Wren, J. D., & Towner, R. A. (2017). ELTD1, an effective anti-angiogenic target for gliomas: Preclinical assessment in mouse GL261 and human G55 xenograft glioma models. Neuro-oncology, 19(2), 175-185. https://doi.org/10.1093/neuonc/now147