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.
N1 - Funding Information:
The Oklahoma Medical Research Foundation (to R.A.T.), the Chapman Foundation (to J.D.W.), and the National Institute of General Medical Sciences of the National Institutes of Health (NIH NIGMS) grant no. 5P20GM103636-02 (to J.D.W.). An Institutional Development Award (IDeA) from the NIH NIGMS, grant no. 5P20GM103639 (to K.-M.F.) for the use of the Histology and Immunohistochemistry Core at the Stephenson Cancer Center, which provided immunohistochemistry and image analysis services, also assisted with funding.
Publisher Copyright:
© The Author(s) 2017.
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
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U2 - 10.1093/neuonc/now147
DO - 10.1093/neuonc/now147
M3 - Article
C2 - 27416955
AN - SCOPUS:85019749335
SN - 1522-8517
VL - 19
SP - 175
EP - 185
JO - Neuro-oncology
JF - Neuro-oncology
IS - 2
ER -