دورية أكاديمية
IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.
العنوان: | IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma. |
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المؤلفون: | Muthupalani S; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA. smuthupalani@stagebio.com.; StageBio, 5930 Main St, Mount Jackson, VA, 22842, USA. smuthupalani@stagebio.com., Annamalai D; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA., Feng Y; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA., Ganesan SM; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA., Ge Z; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA., Whary MT; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA., Nakagawa H; Division of Digestive and Liver Diseases and Herbert Irving Cancer Research Center, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA., Rustgi AK; Division of Digestive and Liver Diseases and Herbert Irving Cancer Research Center, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA., Wang TC; Division of Digestive and Liver Diseases and Herbert Irving Cancer Research Center, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA., Fox JG; Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 16-825C, Cambridge, MA, 02139, USA. Jgfox@mit.edu.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. Jgfox@mit.edu. |
المصدر: | Scientific reports [Sci Rep] 2023 Aug 05; Vol. 13 (1), pp. 12732. Date of Electronic Publication: 2023 Aug 05. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | 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 , Mouth Neoplasms*/genetics , Mouth Neoplasms*/complications, Animals ; Child, Preschool ; Humans ; Mice ; Inflammation/genetics ; Inflammation/complications ; Metaplasia ; Mice, Transgenic ; Squamous Cell Carcinoma of Head and Neck/complications |
مستخلص: | 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. (© 2023. Springer Nature Limited.) |
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معلومات مُعتمدة: | P30 DK132710 United States DK NIDDK NIH HHS; P30 ES002109 United States ES NIEHS NIH HHS; R35 CA210088 United States CA NCI NIH HHS; U54 CA163004 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (IL1B protein, mouse) |
SCR Disease Name: | Adenocarcinoma Of Esophagus |
تواريخ الأحداث: | Date Created: 20230805 Date Completed: 20230807 Latest Revision: 20240123 |
رمز التحديث: | 20240123 |
مُعرف محوري في PubMed: | PMC10404242 |
DOI: | 10.1038/s41598-023-39907-8 |
PMID: | 37543673 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-023-39907-8 |