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

7 Citations (Scopus)

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 - 2017

Fingerprint

Heterografts
Glioma
Therapeutics
Anti-Idiotypic Antibodies
Microvessels
Tumor Burden
Vascular Endothelial Growth Factor A
Antibodies
Angiography
Biomarkers
Immunohistochemistry
Neoplasm Antibodies
Perfusion Imaging
Chromosomes, Human, Pair 1
Glioblastoma
Growth
Computational Biology
Epidermal Growth Factor
Rodentia
Neoplasms

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

Cite this

Ziegler, J., Pody, R., De Souza, P. C., Evans, B., Saunders, D., Smith, N., ... 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

ELTD1, an effective anti-angiogenic target for gliomas : Preclinical assessment in mouse GL261 and human G55 xenograft glioma models. / Ziegler, Jadith; Pody, Richard; De Souza, Patricia Coutinho; Evans, Blake; Saunders, Debra; Smith, Nataliya; Mallory, Samantha; Njoku, Charity; Dong, Yunzhou; Chen, Hong; Dong, Jiali; Lerner, Megan; Mian, Osamah; Tummala, Sai; Battiste, James; Fung, Kar Ming; Wren, Jonathan D.; Towner, Rheal A.

In: Neuro-Oncology, Vol. 19, No. 2, 2017, p. 175-185.

Research output: Contribution to journalArticle

Ziegler, J, Pody, R, De Souza, PC, 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, KM, Wren, JD & Towner, RA 2017, 'ELTD1, an effective anti-angiogenic target for gliomas: Preclinical assessment in mouse GL261 and human G55 xenograft glioma models', Neuro-Oncology, vol. 19, no. 2, pp. 175-185. https://doi.org/10.1093/neuonc/now147
Ziegler, Jadith ; Pody, Richard ; De Souza, Patricia Coutinho ; Evans, Blake ; Saunders, Debra ; Smith, Nataliya ; Mallory, Samantha ; Njoku, Charity ; Dong, Yunzhou ; Chen, Hong ; Dong, Jiali ; Lerner, Megan ; Mian, Osamah ; Tummala, Sai ; Battiste, James ; Fung, Kar Ming ; Wren, Jonathan D. ; Towner, Rheal A. / ELTD1, an effective anti-angiogenic target for gliomas : Preclinical assessment in mouse GL261 and human G55 xenograft glioma models. In: Neuro-Oncology. 2017 ; Vol. 19, No. 2. pp. 175-185.
@article{07a24cd556974bf38765ba6501ac4361,
title = "ELTD1, an effective anti-angiogenic target for gliomas: Preclinical assessment in mouse GL261 and human G55 xenograft glioma models",
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.",
keywords = "Anti-ELTD1 antibody, ELTD1 ([Epidermal Growth Factor (EGF), Gl261 and G55 gliomas, Latrophilin and seven transmembrane domain-containing 1] on chromosome 1), MRI",
author = "Jadith Ziegler and Richard Pody and {De Souza}, {Patricia Coutinho} and Blake Evans and Debra Saunders and Nataliya Smith and Samantha Mallory and Charity Njoku and Yunzhou Dong and Hong Chen and Jiali Dong and Megan Lerner and Osamah Mian and Sai Tummala and James Battiste and Fung, {Kar Ming} and Wren, {Jonathan D.} and Towner, {Rheal A.}",
year = "2017",
doi = "10.1093/neuonc/now147",
language = "English (US)",
volume = "19",
pages = "175--185",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - ELTD1, an effective anti-angiogenic target for gliomas

T2 - Preclinical assessment in mouse GL261 and human G55 xenograft glioma models

AU - Ziegler, Jadith

AU - Pody, Richard

AU - De Souza, Patricia Coutinho

AU - Evans, Blake

AU - Saunders, Debra

AU - Smith, Nataliya

AU - Mallory, Samantha

AU - Njoku, Charity

AU - Dong, Yunzhou

AU - Chen, Hong

AU - Dong, Jiali

AU - Lerner, Megan

AU - Mian, Osamah

AU - Tummala, Sai

AU - Battiste, James

AU - Fung, Kar Ming

AU - Wren, Jonathan D.

AU - Towner, Rheal A.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Anti-ELTD1 antibody

KW - ELTD1 ([Epidermal Growth Factor (EGF)

KW - Gl261 and G55 gliomas

KW - Latrophilin and seven transmembrane domain-containing 1] on chromosome 1)

KW - MRI

UR - http://www.scopus.com/inward/record.url?scp=85019749335&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019749335&partnerID=8YFLogxK

U2 - 10.1093/neuonc/now147

DO - 10.1093/neuonc/now147

M3 - Article

C2 - 27416955

AN - SCOPUS:85019749335

VL - 19

SP - 175

EP - 185

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 2

ER -