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

Oncotarget
Nahir Cortes-SantiagoC Gomez-Manzano

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 and chemotherapy ineffective. Our group has previously reported that Tie2-expressing monocytes (TEMs) are aberrantly present at the tumor/normal brain interface after anti-VEGF therapies and their significant role in the invasive outgrowth of these tumors. Here, we aimed to further understand the mechanisms leading to this pro-invasive tumor microenvironment. Examination of a U87MG xenogeneic glioma model and a GL261 murine syngeneic model showed increased tumor expression of angiopoietin 2 (Ang2), a natural ligand of Tie2, after anti-angiogenesis therapies targeting VEGF or VEGF receptor (VEGFR), as assessed by immunohistochemical analysis, immunofluorescence analysis, and enzyme-linked immunosorbent assays of tumor lysates. Migration and gelatinolytic assays showed that Ang2 acts as both a chemoattractant of TEMs and an enhancing signal for their tumor-remodeling properties. Accordingly, in vivo transduction of Ang2 into intracranial gliomas increased recruitment of TEMs into the tumor. To reduce invasive tumor outgrowt...Continue Reading

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Citations

May 17, 2017·Oncoimmunology·Riccardo TurriniMarie-Agnès Doucey
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Methods Mentioned

BETA
enzyme-linked
xenografts
enzyme-linked immunosorbent assays
xenograft
Fluorescence
Assay
ELISA

Software Mentioned

GraphPad
GraphPad Prism

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