ArticleThe Journal of clinical investigation2016
Targeting prion-like protein doppel selectively suppresses tumor angiogenesis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Doppel as an early-stage biomarker promoting EMT and dissemination in ovarian cancers.International journal of cancer · 2026Article
- Selective Targeting of Tip Endothelial Cells as a Therapeutic Strategy for Tumor Angiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomedical applications of engineered heparin-based materials.Bioactive materials · 2024Review
- Secretogranin III stringently regulates pathological but not physiological angiogenesis in oxygen-induced retinopathy.Cellular and molecular life sciences : CMLS · 2022Article
- The Cellular Prion Protein and the Hallmarks of Cancer.Cancers · 2021Review
- Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice.Neuroscience · 2021Article
- Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.Frontiers in genetics · 2021Article
- Molecular Targeting of VEGF with a Suramin Fragment-DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins.Biomolecules · 2020Article
- The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier development.Development (Cambridge, England) · 2020Article
- Runx3 regulates chondrocyte phenotype by controlling multiple genes involved in chondrocyte proliferation and differentiation.Molecular biology reports · 2020Article
- Activating CD137 Signaling Promotes Sprouting Angiogenesis via Increased VEGFA Secretion and the VEGFR2/Akt/eNOS Pathway.Mediators of inflammation · 2020Article
- Emerging Role of Cellular Prion Protein in the Maintenance and Expansion of Glioma Stem Cells.Cells · 2019Review
- Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety.Angiogenesis · 2019Article
- Secretogranin III: a diabetic retinopathy-selective angiogenic factor.Cellular and molecular life sciences : CMLS · 2018Review
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- Anticancer drugs: Tumour-specific angiogenesis inhibition.Nature reviews. Drug discovery · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Controlled and site-specific regulation of growth factor signaling remains a major challenge for current antiangiogenic therapies, as these antiangiogenic agents target normal vasculature as well tumor vasculature. In this article, we identified the prion-like protein doppel as a potential therapeutic target for tumor angiogenesis. We investigated the interactions between doppel and VEGFR2 and evaluated whether blocking the doppel/VEGFR2 axis suppresses the process of angiogenesis. We discovered that tumor endothelial cells (TECs), but not normal ECs, express doppel; tumors from patients and mouse xenografts expressed doppel in their vasculatures. Induced doppel overexpression in ECs enhanced vascularization, whereas doppel constitutively colocalized and complexed with VEGFR2 in TECs. Doppel inhibition depleted VEGFR2 from the cell membrane, subsequently inducing the internalization and degradation of VEGFR2 and thereby attenuating VEGFR2 signaling. We also synthesized an orally active glycosaminoglycan (LHbisD4) that specifically binds with doppel. We determined that LHbisD4 concentrates over the tumor site and that genetic loss of doppel in TECs decreases LHbisD4 binding and targeting both in vitro and in vivo. Moreover, LHbisD4 eliminated VEGFR2 from the cell membrane, prevented VEGF binding in TECs, and suppressed tumor growth. Together, our results demonstrate that blocking doppel can control VEGF signaling in TECs and selectively inhibit tumor angiogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.