title: ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models.
abstract: 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 domain-containing 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.|Department of Pathology, Oklahoma City, Oklahoma.
authors.forename: Jadith
authors.initials: J
authors.lastname: Ziegler
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Richard
authors.initials: R
authors.lastname: Pody
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Patricia
authors.initials: P
authors.lastname: Coutinho de Souza
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Blake
authors.initials: B
authors.lastname: Evans
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Debra
authors.initials: D
authors.lastname: Saunders
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Smith
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.|The University of Oklahoma Children's Hospital, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Samantha
authors.initials: S
authors.lastname: Mallory
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Charity
authors.initials: C
authors.lastname: Njoku
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Karp Family Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Karp Family Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Jiali
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Surgery Research Laboratory, Oklahoma City, Oklahoma.
authors.forename: Megan
authors.initials: M
authors.lastname: Lerner
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Osamah
authors.initials: O
authors.lastname: Mian
authors.affiliation: Comparative Medicine, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Sai
authors.initials: S
authors.lastname: Tummala
authors.affiliation: The Stephenson Cancer Center, Oklahoma City, Oklahoma.
authors.forename: James
authors.initials: J
authors.lastname: Battiste
authors.affiliation: The Stephenson Cancer Center, Oklahoma City, Oklahoma.|Department of Pathology, Oklahoma City, Oklahoma.
authors.forename: Kar-Ming
authors.initials: KM
authors.lastname: Fung
authors.affiliation: Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.|Department of Biochemistry and Molecular Biology, Oklahoma City, Oklahoma.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wren
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.|The Stephenson Cancer Center, Oklahoma City, Oklahoma.|Department of Pathology, Oklahoma City, Oklahoma.
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C428324:ADGRL4 protein, human; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D043562:Receptors, G-Protein-Coupled
keywords: ELTD1 ([epidermal growth factor (EGF); GL261 and G55 gliomas; MRI; anti-ELTD1 antibody; latrophilin and seven transmembrane domain-containing 1] on chromosome 1)