ArticleBMC cancer2017
Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.
Article in BMC cancer, 2017. 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.
- Article
- Celebrating the 1945 JNCI pioneering contribution to antiangiogenic therapy for cancer.Journal of the National Cancer Institute · 2024Article
- Article
- Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug.iScience · 2023Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cellsFrontiers in oncology · 2022Article
- Review
- Vascular normalisation as the stepping stone into tumour microenvironment transformation.British journal of cancer · 2021Review
- Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer.International journal of nanomedicine · 2021Review
- Novel Pathways for Targeting Tumor Angiogenesis in Metastatic Breast Cancer.Frontiers in oncology · 2021Review
- TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury.Molecular brain · 2020Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells.Clinical & experimental metastasis · 2019Article
- Co-Expression Analysis Reveals Mechanisms Underlying the Varied Roles of NOTCH1 in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019Article
- Article
- Intriguing Roles for Endothelial ADAM10/Notch Signaling in the Development of Organ-Specific Vascular Beds.Physiological reviews · 2018Review
- Drug Resistance in Non-Small Cell Lung Cancer: A Potential for NOTCH Targeting?Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models.
methodsWe used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas.
resultsWe found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy.
conclusionsBy reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.
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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.