Article ; Online: IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.
2023 Volume 13, Issue 1, Page(s) 12732
Abstract: Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human ... ...
| Abstract | Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett's esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive. We report for the first time that in addition to the previously described Barrett's esophagus-like metaplasia, the L2-IL-1β mice also develop squamous epithelial dysplasia with progression to squamous cell carcinoma (SCC) in the esophagus and the tongue. L2-IL-1β showed age-dependent progression of squamous dysplasia to SCC with approximately 40% (n = 49) and 23.5% (n = 17) incidence rates for esophageal and tongue invasive SCC respectively, by 12-15 months of age. Interestingly, SCC development and progression in L2-IL-1β was similar in both Germ Free (GF) and Specific Pathogen Free (SPF) conditions. Immunohistochemistry revealed a T cell predominant inflammatory profile with enhanced expression of Ki67, Sox2 and the DNA double-strand break marker, γ-H2AX, in the dysplastic squamous epithelia of L2-IL-1β mice. Pro-inflammatory cytokines, immunomodulatory players, chemoattractants for inflammatory cells (T cells, neutrophils, eosinophils, and macrophages) and oxidative damage marker, iNOS, were significantly increased in the esophageal and tongue tissues of L2-IL-1β mice. Our recent findings have expanded the translational utility of the IL-1β mouse model to aid in further characterization of the key pathways of inflammation driven BE and EAC as well as ESCC and Oral SCC. |
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| MeSH term(s) | Animals ; Child, Preschool ; Humans ; Mice ; Adenocarcinoma/pathology ; Barrett Esophagus/pathology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/complications ; Esophageal Neoplasms/pathology ; Esophageal Squamous Cell Carcinoma/genetics ; Head and Neck Neoplasms/complications ; Inflammation/genetics ; Inflammation/complications ; Metaplasia ; Mice, Transgenic ; Mouth Neoplasms/genetics ; Mouth Neoplasms/complications ; Squamous Cell Carcinoma of Head and Neck/complications |
| Chemical Substances | IL1B protein, mouse |
| Language | English |
| Publishing date | 2023-08-05 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-023-39907-8 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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