ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
The vascular delta-like ligand-4 (DLL4)-Notch4 signaling correlates with angiogenesis in primary glioblastoma: an immunohistochemical study.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Exploiting the Notch pathway in HTLV-1-driven adult T-cell leukemia/lymphoma: a mini-review.Annals of hematology · 2026Review
- NOTCH4 as a driver of epithelial-mesenchymal transition, angiogenesis, and stromal remodeling in lung adenocarcinoma: integrated transcriptomic and protein-level validation.Translational lung cancer research · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- S3RL: Enhancing Spatial Single-Cell Transcriptomics With Separable Representation Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.Current pharmaceutical design · 2026Review
- Notch2/3-DLL4 interaction in urothelial cancer cell lines supports a tumorigenic role of Notch signaling pathways in bladder carcinoma.PloS one · 2025Article
- Assessment of blood-brain barrier injury in hypertensive CSVD by 11.7TMR T1mapping and microvascular pathologic changes.Metabolic brain disease · 2024Article
- Nogo-B promotes angiogenesis and improves cardiac repair after myocardial infarction via activating Notch1 signaling.Cell death & disease · 2022Article
- Proteomic Distributions in CD34+ Microvascular Niche Patterns of Glioblastoma.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Preliminary Research of Main Components of Dll4/ Notch-VEGF Signaling Pathway Under High-Glucose Stimulation in vitro.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives.Cancer management and research · 2021Review
- Contradictory Effect of Notch1 and Notch2 on Phosphatase and Tensin Homolog and its Influence on Glioblastoma Angiogenesis.Galen medical journal · 2021Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Vascular endothelial growth factor 165 inhibits pro-fibrotic differentiation of stromal cells via the DLL4/Notch4/smad7 pathway.Cell death & disease · 2019Article
- Glioma Stem Cell Niches in Human Glioblastoma Are Periarteriolar.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- Notch4 inhibition suppresses invasion and vasculogenic mimicry formation of hepatocellular carcinoma cells.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
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- Notch signaling in lung diseases: focus on Notch1 and Notch3.Therapeutic advances in respiratory disease · 2016Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delta-like ligand-4 (DLL4)-Notch signaling is known to play a pivotal role in the regulation of tumor angiogenesis. We had previously found that DLL4 was overexpressed, while Notch1 receptor, which binds to DLL4 during angiogenesis, was absent in the majority of human primary glioblastomas. Thus, DLL4-Notch signaling pathway in the regulation of tumor angiogenesis in primary glioblastoma remains unknown. Tumor tissues from 70 patients with primary glioblastoma were analyzed by immunohistochemistry for expression of components of DLL4-Notch signaling, vascular endothelial growth factor (VEGF), and microvessel density (MVD). Immunohistochemistry results showed that the positive staining of DLL4 and Notch4 was primarily distributed in tumor vascular endothelial cells but rarely detected in tumor cells. However, VEGF, hairy/enhancer of split-1 (HES1; a target gene of Notch signaling), and Notch1-3 expression was seen in both tumor vascular endothelial cells and tumor cells. Univariate analysis showed that the expression levels of VEGF and DLL4, HES1, and Notch4 in tumor endothelial cells were significantly associated with MVD in primary glioblastoma (P < 0.001). Binary logistic regression analysis showed that high expression levels of DLL4, HES1, and Notch4 in tumor endothelial cells were associated with a decrease of MVD in primary glioblastoma, while MVD increased with elevated VEGF expression in contrast. In addition, DLL4, Notch4, and HES1 expression were positively correlated in tumor vascular endothelial cells (P < 0.05). We conclude that the vascular DLL4-Notch4 signaling and VEGF signaling complementing each other plays an important role in the progression of tumor angiogenesis in primary glioblastoma. Graphical abstract A, positive staining of DLL4 in human kidney; B, positive staining of VEGF in human breast cancer; C, positive staining of CD34 in human lung cancer; D, positive staining of HES1 in human breast cancer; E-H, positive staining of Notch1-4: E-F in human lung cancer; G-H in human kidney.
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