ArticleNeoplasia (New York, N.Y.)2015
EGFR regulates the development and microarchitecture of intratumoral angiogenic vasculature capable of sustaining cancer cell intravasation.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Prognostic Significance of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Tumor-Associated Neutrophils in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Pooled it
- Association between the expression of specific microRNAs and prostate cancer progression- a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Innovative immunotherapeutic strategies for thyroid cancer: challenges and opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Immunohistochemical evaluation of EGFR protein expression and microvascular density reveals an angiogenic signature in Tunisian patients with metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.Cancer metastasis reviews · 2026Review
- PHLDA1 silencing in IMR-32 human neuroblastoma cells results in ABCB1 overexpression, augments chemoresistance and leads to increased growth of tumors.Scientific reports · 2025Article
- Multiomics Analysis Reveals Molecular Changes during Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers.Cancer research · 2025Article
- The Comparative Effect of Morphine on Proliferation of Cancer Cell Lines Originating from Different Organs: An In Vitro Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Neutrophil diversity is associated with T-cell immunity and clinical relevance in patients with thyroid cancer.Cell death discovery · 2024Article
- Tumor-associated macrophages in colorectal cancer metastasis: molecular insights and translational perspectives.Journal of translational medicine · 2024Review
- Biological Roles and Clinical Therapeutic Applications of Tumor-Associated Macrophages in Colorectal Liver Metastasis.Journal of inflammation research · 2024Review
- Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies.Life (Basel, Switzerland) · 2023Review
- Deciphering the Precise Target for Saroglitazar Associated Antiangiogenic Effect: A Computational Synergistic Approach.ACS omega · 2023Article
- Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis.Molecular biology reports · 2023Article
- Significance of circulating tumor cells in lung cancer: a narrative review.Translational lung cancer research · 2023Review
- Diverse Neutrophil Functions in Cancer and Promising Neutrophil-Based Cancer Therapies.International journal of molecular sciences · 2022Review
- Alpinumisoflavone against cancer pro-angiogenic targets: In silico, In vitro, and In ovo evaluation.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Article
- Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion.Stem cells translational medicine · 2022Article
- Studying molecular signaling in major angiogenic diseases.Molecular and cellular biochemistry · 2022Review
- Prognostic factors for relapse-free survival in stage IB-IIIA primary lung adenocarcinoma by epidermal growth factor receptor mutation status.BMC cancer · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Many malignant characteristics of cancer cells are regulated through pathways induced by the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Herein, we show that besides directly affecting the biology of cancer cells per se, EGFR also regulates the primary tumor microenvironment. Specifically, our findings demonstrate that both the expression and signaling activity of EGFR are required for the induction of a distinct intratumoral vasculature capable of sustaining tumor cell intravasation, a critical rate-limiting step in the metastatic cascade. An intravasation-sustaining mode of intratumoral angiogenic vessels depends on high levels of tumor cell EGFR and the interplay between EGFR-regulated production of interleukin 8 by tumor cells, interleukin-8-induced influx of tumor-infiltrating neutrophils delivering their unique matrix metalloproteinase-9, and neutrophil matrix metalloproteinase-9-dependent release of the vascular permeability and endothelial growth factor, VEGF. Our data indicate that through VEGF-mediated disruption of endothelial layer integrity and increase of intratumoral vasculature permeability, EGFR activity significantly facilitates active intravasation of cancer cells. Therefore, this study unraveled an important but overlooked function of EGFR in cancer, namely, its ability to create an intravasation-sustaining microenvironment within the developing primary tumor by orchestrating several interrelated processes required for the initial steps of cancer metastasis through vascular routes. Our findings also suggest that EGFR-targeted therapies might be more effective when implemented in cancer patients with early-staged primary tumors containing a VEGF-dependent angiogenic vasculature. Accordingly, early EGFR inhibition combined with various anti-VEGF approaches could synergistically suppress tumor cell intravasation through inhibiting the highly permeable angiogenic vasculature induced by EGFR-overexpressing aggressive cancer cells.
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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.