ArticleExperimental & molecular medicine2023
An agonistic anti-Tie2 antibody suppresses the normal-to-tumor vascular transition in the glioblastoma invasion zone.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- Glioma-Associated Microglia Augment Neuronal Hyper-Excitability in Glioma.Brain tumor research and treatment · 2026Review
- A novel Tie2xVEGF bispecific antibody fusion demonstrates enhanced therapeutic efficacy through direct Tie2 activation and VEGF neutralization.Journal of translational medicine · 2026Article
- TIE2 links MEKK3-KLF2/4 and PI3K signaling in cerebral cavernous malformation.The Journal of experimental medicine · 2026Article
- Review
- Review
- Review
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.Biologics : targets & therapy · 2026Review
- Tie2 activator 4E2 ameliorates diabetic nephropathy and synergizes with dapagliflozin in a mouse model.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Risk Factors Involved in the Blood (Leukocyte-Depleted Suspended Red Blood Cells and Plasma) Transfusion During Glioma Operations.Journal of blood medicine · 2025Article
- Article
- Antiangiogenic-immune-checkpoint inhibitor combinations: lessons from phase III clinical trials.Nature reviews. Clinical oncology · 2024Review
- Milestones in tumor vascularization and its therapeutic targeting.Nature cancer · 2024Review
- Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.Clinical and translational medicine · 2024Review
- CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review.Biomedicines · 2024Article
- Vascularization ability of glioma stem cells in different three-dimensional microenvironments.Regenerative biomaterials · 2024Article
- Intraoperative radiotherapy in breast cancer: Alterations to the tumor microenvironment and subsequent biological outcomes (Review).Molecular medicine reports · 2023Review
- A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease.Science advances · 2023Article
- Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor progression is intimately associated with the vasculature, as tumor proliferation induces angiogenesis and tumor cells metastasize to distant organs via blood vessels. However, whether tumor invasion is associated with blood vessels remains unknown. As glioblastoma (GBM) is featured by aggressive invasion and vascular abnormalities, we characterized the onset of vascular remodeling in the diffuse tumor infiltrating zone by establishing new spontaneous GBM models with robust invasion capacity. Normal brain vessels underwent a gradual transition to severely impaired tumor vessels at the GBM periphery over several days. Increasing vasodilation from the tumor periphery to the tumor core was also found in human GBM. The levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) showed a spatial correlation with the extent of vascular abnormalities spanning the tumor-invading zone. Blockade of VEGFR2 suppressed vascular remodeling at the tumor periphery, confirming the role of VEGF-VEGFR2 signaling in the invasion-associated vascular transition. As angiopoietin-2 (ANGPT2) was expressed in only a portion of the central tumor vessels, we developed a ligand-independent tunica interna endothelial cell kinase 2 (Tie2)-activating antibody that can result in Tie2 phosphorylation in vivo. This agonistic anti-Tie2 antibody effectively normalized the vasculature in both the tumor periphery and tumor center, similar to the effects of VEGFR2 blockade. Mechanistically, this antibody-based Tie2 activation induced VE-PTP-mediated VEGFR2 dephosphorylation in vivo. Thus, our study reveals that the normal-to-tumor vascular transition is spatiotemporally associated with GBM invasion and may be controlled by Tie2 activation via a novel mechanism of action.
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