ArticlePLoS biology2016
EDA-Fibronectin Originating from Osteoblasts Inhibits the Immune Response against Cancer.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 39 citations in OpenAlex.
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- 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
- Roles of focal adhesion proteins in skeleton and diseases.Acta pharmaceutica Sinica. B · 2023Review
- Targeting the extra domain A of fibronectin for cancer therapy with CAR-T cells.Journal for immunotherapy of cancer · 2022Article
- Recent Progress on the Role of Fibronectin in Tumor Stromal Immunity and Immunotherapy.Current topics in medicinal chemistry · 2022Review
- Elevated plasma EDA fibronectin in primary myelofibrosis is determined by high allele burden ofFrontiers in oncology · 2022Article
- Beyond immunosuppressive effects: dual roles of myeloid-derived suppressor cells in bone-related diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Novel approaches to target the microenvironment of bone metastasis.Nature reviews. Clinical oncology · 2021Review
- Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis.Biomolecules · 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
- Review
- Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies.Frontiers in immunology · 2021Review
- Fibronectin and Its Receptors in Hematopoiesis.Cells · 2020Review
- Interplay between aging, lung inflammation/remodeling, and fibronectin EDA in lung cancer progression.Cancer biology & therapy · 2020Article
- The systemic control of cancers by the osteoblasts.Oncoscience · 2018Article
- HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Fibronectins containing extradomain A or B enhance osteoblast differentiation via distinct integrins.The Journal of biological chemistry · 2017Article
- Fibronectin: How Its Aberrant Expression in Tumors May Improve Therapeutic Targeting.Journal of Cancer · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoblasts lining the inner surface of bone support hematopoietic stem cell differentiation by virtue of proximity to the bone marrow. The osteoblasts also modify their own differentiation by producing various isoforms of fibronectin (FN). Despite evidence for immune regulation by osteoblasts, there is limited knowledge of how osteoblasts modulate cells of the immune system. Here, we show that extra domain A (EDA)-FN produced by osteoblasts increases arginase production in myeloid-derived cells, and we identify α5β1 as the mediating receptor. In different mouse models of cancer, osteoblasts or EDA-FN was found to up-regulate arginase-1 expression in myeloid-derived cells, resulting in increased cancer growth. This harmful effect can be reduced by interfering with the integrin α5β1 receptor or inhibiting arginase. Conversely, in tissue injury, the expression of arginase-1 is normally beneficial as it dampens the immune response to allow wound healing. We show that EDA-FN protects against excessive fibrotic tissue formation in a liver fibrosis model. Our results establish an immune regulatory function for EDA-FN originating from the osteoblasts and identify new avenues for enhancing the immune reaction against cancer.
Identifiers
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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.