Gliomas consist of up to 80% of malignant brain tumors that are invasive and typically resistant to radiotherapy and chemotherapy. Finding biomarkers to high-grade gliomas can enable better diagnosis and therapeutic intervention for this disease. We have identified ELTD1 as a biomarker for high-grade human gliomas. Here, we report our findings in vivo using anti-ELTD1 (at two different concentrations), Bevacizumab, and IgG antibodies on human G55 xenograft glioma models. Using MRI, we investigate tumor growth, perfusion, tumor blood flow, and microvessel density changes in mice. In addition, survival rates were measured.
Mice were implanted with human G55 xenograft glioma cells and were left untreated, administered anti-ELTD1, (1 mg/kg or 2 mg/kg every 2-3 days) Bevacizumab (2 mg/kg every 2-3 days) or IgG (1 mg/kg every 2-3 days). MRI experiments were performed to assess tumor growth and calculate tumor volumes. In order to assess angiogenesis, representative histology slides were obtained and stained for blood vessels using CD34 antibody and microvessel density (MVD) was then calculated. Finally, cerebral blood flow rates from MR perfusion imaging was obtained as well as MR angiography to determine tumor blood volume from mice in each group.
Our results show a significant decrease in tumor volumes and increase in percent survival for mice treated with 1 mg/kg and 2 mg/kg of ELTD1 antibody compared to untreated mice and IgG treated mice. Mice also had an increase in perfusion, decrease in tumor blood volume and decrease in MVD. Anti-ELTD1 antibody therapy reduced tumor volumes, prolonged life, and overall decreased angiogenesis in our mouse model. Anti-ELTD1 therapy may be an ideal anti-angiogenic treatment for high-grade gliomas.
Citation Format: Jadith Ziegler, Nataliya Smith, Debra Saunders, Blake Evans, James D. Battiste, Michael Sughrue, Paul Tompkins, Jake Sutton, Megan Lerner, Patricia Coutinho de Souza, Kar-Ming Fung, Jonathan Wren, Rheal Towner. Eltd1 as an anti-angiogenic therapy against glioma tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3267.