Soluble Tie2 overrides the heightened invasion induced by anti-angiogenesis therapies in gliomas

• DOI: 10.18632/oncotarget.7550
• Publication Date: 2016-02-21T12:19:54Z
• Authors: Nahir Cortes-Sant...; Mohammad B. Hossain; Konrad Gabrusiewicz; Xuejun Fan; Joy Gumin; Frank C. Marini; Marta M. Alonso; Frederick Lang; W.K. Yung; Juan Fueyo; Candelaria Gomez-...
• Keywords: Angiopoietin receptor

// Nahir Cortes-Santiago 1, 6 , Mohammad B. Hossain 1 Konrad Gabrusiewicz Xuejun Fan Joy Gumin 2 Frank C. Marini 3 Marta M. Alonso 4 Frederick Lang W.K. Yung Juan Fueyo Candelaria Gomez-Manzano 5, Department of Neuro-Oncology, The University Texas MD Anderson Cancer Center, Houston, TX, USA Neurosurgery, Comprehensive Wake Forest University, Winston-Salem, NC, Medical Oncology, Hospital Navarra, Pamplona, Spain 5 Genetics, Biology Program, Graduate School Biomedical Sciences at Correspondence to: Gomez-Manzano, e-mail: [e-mail] Keywords: anti-angiogenesis, glioma, invasion, angiopoietin 2, Tie2-expressing monocytes Received: November 10, 2015 Accepted: January 29, 2016 Published: February 21, ABSTRACT Glioblastoma recurrence after treatment with the anti–vascular endothelial growth factor (VEGF) agent bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision chemotherapy ineffective. Our group has previously reported (TEMs) are aberrantly present tumor/normal brain interface anti-VEGF therapies their significant role in invasive outgrowth these tumors. Here, we aimed to further understand mechanisms leading this pro-invasive tumor microenvironment. Examination U87MG xenogeneic glioma model GL261 murine syngeneic showed increased expression (Ang2), natural ligand Tie2, anti-angiogenesis targeting VEGF or receptor (VEGFR), as assessed immunohistochemical analysis, immunofluorescence enzyme-linked immunosorbent assays lysates. Migration gelatinolytic Ang2 acts both chemoattractant TEMs an enhancing signal for tumor-remodeling properties. Accordingly, vivo transduction into intracranial gliomas recruitment tumor. To reduce therapy, targeted Ang-Tie2 axis using Tie2 decoy receptor. Using models, observed overexpression soluble within prevented development invasion treatment. Taken together, data indicate active Ang2-Tie2 pathway provide rationale testing combined pathways patients glioblastoma.