ArticleMedical oncology (Northwood, London, England)2014
Delta-like ligand 4 (DLL4) in the plasma and neoplastic tissues from breast cancer patients: correlation with metastasis.
Article in Medical oncology (Northwood, London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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
25 citing papers in PubMed.
- Nanomaterials for delivery of drugs and genes to disrupt notch signaling pathway in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2Journal for immunotherapy of cancer · 2024Article
- Beauvericin Reverses Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer Cells through Regulation of Notch Signaling and Autophagy.ACS pharmacology & translational science · 2024Article
- The Prediction of DLL4 as a Prognostic Biomarker in Patients with Gastric Cancer Using Anti-DLL4 Nanobody.Journal of gastrointestinal cancer · 2024Article
- Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome.Infection · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.Acta pharmaceutica Sinica. B · 2023Review
- Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer.Journal of pathology and translational medicine · 2023Article
- [JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance.International journal of molecular sciences · 2022Review
- Notch signaling sculpts the stem cell niche.Frontiers in cell and developmental biology · 2022Review
- Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.Oxidative medicine and cellular longevity · 2022Review
- Review
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- The many facets of Notch signaling in breast cancer: toward overcoming therapeutic resistance.Genes & development · 2020Review
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- The Complexities of Metastasis.Cancers · 2019Review
- Notch signaling in breast cancer: From pathway analysis to therapy.Cancer letters · 2019Review
- FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.BMC cancer · 2019Article
- High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.Journal of Cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delta-like ligand 4 (DLL4) is a ligand of the notch pathway. In tumor angiogenesis, DLL4 switches to vascular maturation by providing a negative feedback on VEGFR2 activity. We investigated the expression of DLL4 in the plasma and cancer tissues from breast cancer patients. Plasma samples were collected from 18 women with localized breast cancer, six women with benign breast disease and from six patients with widespread metastatic disease. DLL4 was assessed using ELISA and in cancer tissues using immunohistochemistry. Patients with metastatic breast cancer had significantly higher levels (median 6.7 ± 0.81 ng/ml) compared to patients with localized tumors (median 5.4 ± 0.70 ng/ml) (p = 0.005) and to patients with benign breast disease (median 4.3 ± 0.28) (p = 0.0003). High histology grade was significantly linked with higher plasma DLL4 levels (median 5.59 ± 0.62 vs. 5.12 ± 0.44 ng/ml; p = 0.01). Surgical removal of high-grade breast cancer resulted in significant reduction in DLL4 plasma levels (p = 0.003). DLL4 was expressed in tumor-associated vessels and in cancer cells. The ratio of DLL4+/CD31+ vascular density (VD) ranged from 23 to 88% (median 49 %). High DLL4 cancer cell expression and high DLL4+ VD were significantly linked with nodal involvement (p = 0.004 and 0.01, respectively). Linear regression analysis showed a significant association of DLL4 plasma levels with the percentage of DLL4+ cancer cells (p = 0.03, r = 0.50) and with DLL4+ VD (p = 0.0007, r = 0.60). It is concluded that DLL4 is overexpressed in breast cancer cells and breast cancer vasculature and is linked with nodal and distant metastasis. DLL4 plasma levels measurement can reliably estimate the total DLL4 breast cancer/vasculature activity.
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