ArticleScientific reports2015
The TLR4 agonist fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer vaccine.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
- EDA Fibronectin Microarchitecture and YAP Translocation During Wound Closure.bioRxiv : the preprint server for biology · 2024Article
- Insights into the Tumor Microenvironment-Components, Functions and Therapeutics.International journal of molecular sciences · 2023Review
- A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins.NPJ Regenerative medicine · 2023Article
- Dimerization of Transmembrane Proteins in Cancer Immunotherapy.Membranes · 2023Review
- How the mechanobiology orchestrates the iterative and reciprocal ECM-cell cross-talk that drives microtissue growth.Science advances · 2023Article
- A positive feedback loop driven by fibronectin and IL-1β sustains the inflammatory microenvironment in breast cancer.Breast cancer research : BCR · 2023Article
- Article
- Fibronectin containing alternatively spliced extra domain A interacts at the central and c-terminal domain of Toll-like receptor-4.Scientific reports · 2022Article
- ED-B-Containing Isoform of Fibronectin in Tumor Microenvironment of Thymomas: A Target for a Theragnostic Approach.Cancers · 2022Article
- Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer.International journal of molecular sciences · 2022Review
- Recent Progress on the Role of Fibronectin in Tumor Stromal Immunity and Immunotherapy.Current topics in medicinal chemistry · 2022Review
- Identification of splice regulators of fibronectin-EIIIA and EIIIB by direct measurement of exon usage in a flow-cytometry based CRISPR screen.Scientific reports · 2021Article
- The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.Nucleic acids research · 2021Article
- The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy.International journal of molecular sciences · 2021Review
- Design and Evaluation of a Polypeptide that Mimics the Integrin Binding Site for EDA Fibronectin to Block Profibrotic Cell Activity.International journal of molecular sciences · 2021Article
- Alternative Splicing of FN (Fibronectin) Regulates the Composition of the Arterial Wall Under Low Flow.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing.Nature biomedical engineering · 2020Article
- Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing.Science advances · 2020Article
- Shaping Up the Tumor Microenvironment With Cellular Fibronectin.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibronectin (FN) is an extracellular matrix (ECM) protein including numerous fibronectin type III (FNIII) repeats with different functions. The alternatively spliced FN variant containing the extra domain A (FNIII EDA), located between FNIII 11 and FNIII 12, is expressed in sites of injury, chronic inflammation, and solid tumors. Although its function is not well understood, FNIII EDA is known to agonize Toll-like receptor 4 (TLR4). Here, by producing various FN fragments containing FNIII EDA, we found that FNIII EDA's immunological activity depends upon its local intramolecular context within the FN chain. N-terminal extension of the isolated FNIII EDA with its neighboring FNIII repeats (FNIII 9-10-11) enhanced its activity in agonizing TLR4, while C-terminal extension with the native FNIII 12-13-14 heparin-binding domain abrogated it. In addition, we reveal that an elastase 2 cleavage site is present between FNIII EDA and FNIII 12. Activity of the C-terminally extended FNIII EDA could be restored after cleavage of the FNIII 12-13-14 domain by elastase 2. FN being naturally bound to the ECM, we immobilized FNIII EDA-containing FN fragments within a fibrin matrix model along with antigenic peptides. Such matrices were shown to stimulate cytotoxic CD8(+) T cell responses in two murine cancer models.
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