ArticleJournal of immunology and regenerative medicine2021
The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation.
Article in Journal of immunology and regenerative medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Esophagus extracellular matrix with microenvironmental complexity for esophageal organoids.Bioactive materials · 2026Article
- Cardiac matrix-bound Nanovesicles provide insight into mechanisms of clinical heart disease progression to failure.International journal of cardiology · 2025Article
- Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis.Science advances · 2024Article
- Characterization of a decellularized pericardium extracellular matrix hydrogel for regenerative medicine: insights on animal-to-animal variability.Frontiers in bioengineering and biotechnology · 2024Article
- Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- The Study of the Extracellular Matrix in Chronic Inflammation: A Way to Prevent Cancer Initiation?Cancers · 2022Review
- Bio-Engineered Scaffolds Derived from Decellularized Human Esophagus for Functional Organ Reconstruction.Cells · 2022Article
- Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis.NPJ Regenerative medicine · 2022Article
- Article
- Decellularization of tumours: A new frontier in tissue engineering.Journal of tissue engineeringReview
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 3 countries.
Funding
Abstract
introductionMacrophages are capable of extreme plasticity and their activation state has been strongly associated with solid tumor growth progression and regression. Although the macrophage response to extracellular matrix (ECM) isolated from normal tissue is reasonably well understood, there is a relative dearth of information regarding their response to ECM isolated from chronically inflamed tissues, pre-neoplastic tissues, and neoplastic tissues. Esophageal adenocarcinoma (EAC) is a type of neoplasia driven by chronic inflammation in the distal esophagus, and the length of the esophagus provides the opportunity to investigate macrophage behavior in the presence of ECM isolated from a range of disease states within the same organ.
methodsNormal, metaplastic, and neoplastic ECM hydrogels were prepared from decellularized EAC tissue. The hydrogels were evaluated for their nanofibrous structure (SEM), biochemical profile (targeted and global proteomics), and direct effect upon macrophage (THP-1 cell) activation state (qPCR, ELISA, immunolabeling) and indirect effect upon epithelial cell (Het-1A) migration (Boyden chamber).
resultsNanofibrous ECM hydrogels from the three tissue types could be formed, and normal and neoplastic ECM showed distinctive protein profiles by targeted and global mass spectroscopy. ECM proteins functionally related to cancer and tumorigenesis were identified in the neoplastic esophageal ECM including collagen alpha-1(VIII) chain (COL8A1), lumican, and elastin. Metaplastic and neoplastic esophageal ECM induce distinctive effects upon THP-1 macrophage signaling compared to normal esophageal ECM. These effects include activation of pro-inflammatory IFNγ and TNFα gene expression and anti-inflammatory IL1RN gene expression. Most notably, neoplastic ECM robustly increased macrophage TNFα protein expression. The secretome of macrophages pre-treated with metaplastic and neoplastic ECM increases the migration of normal esophageal epithelial cells, similar behavior to that shown by tumor cells. Metaplastic ECM shows similar but less pronounced effects than neoplastic ECM suggesting the abnormal signals also exist within the pre-cancerous state.
conclusionA progressively diseased ECM, as exists within the esophagus exposed to chronic gastric reflux, can provide insights into novel biomarkers of early disease and identify potential therapeutic targets.
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