Inflammation promotes aging-associated oncogenesis in the lung.
| العنوان: | Inflammation promotes aging-associated oncogenesis in the lung. |
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| المؤلفون: | Pham-Danis C; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Chia SB; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Scarborough HA; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Danis E; Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Nemkov T; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Kleczko EK; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Navarro A; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Goodspeed A; Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Bonney EA; Department of Obstetrics, Gynecology and Reproductive Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, United States., Dinarello CA; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Marchetti C; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Nemenoff RA; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Hansen K; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., DeGregori J; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.; Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.; Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 05. Date of Electronic Publication: 2024 Mar 05. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Background: Lung cancer is the leading cause of cancer death in the world. While cigarette smoking is the major preventable factor for cancers in general and lung cancer in particular, old age is also a major risk factor. Aging-related chronic, low-level inflammation, termed inflammaging, has been widely documented; however, it remains unclear how inflammaging contributes to increased lung cancer incidence. Aim : To establish connections between aging-associated changes in the lungs and cancer risk. Methods: We analyzed public databases of gene expression for normal and cancerous human lungs and used mouse models to understand which changes were dependent on inflammation, as well as to assess the impact on oncogenesis. Results: Analyses of GTEx and TCGA databases comparing gene expression profiles from normal lungs, lung adenocarcinoma, lung squamous cell carcinoma of subjects across age groups revealed upregulated pathways such as inflammatory response, TNFA signaling via NFκB, and interferon-gamma response. Similar pathways were identified comparing the gene expression profiles of young and old mouse lungs. Transgenic expression of alpha 1 antitrypsin (AAT) partially reverses increases in markers of aging-associated inflammation and immune deregulation. Using an orthotopic model of lung cancer using cells derived from EML4-ALK fusion-induced adenomas, we demonstrated an increased tumor outgrowth in lungs of old mice while NLRP3 knockout in old mice decreased tumor volumes, suggesting that inflammation contributes to increased lung cancer development in aging organisms. Conclusions: These studies reveal how expression of an anti-inflammatory mediator (AAT) can reduce some but not all aging-associated changes in mRNA and protein expression in the lungs. We further show that aging is associated with increased tumor outgrowth in the lungs, which may relate to an increased inflammatory microenvironment. |
| معلومات مُعتمدة: | I01 BX004495 United States BX BLRD VA; P30 CA046934 United States CA NCI NIH HHS; T32 CA174648 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: aging; inflammation; lung cancer; microenvironment |
| تواريخ الأحداث: | Date Created: 20240318 Latest Revision: 20240325 |
| رمز التحديث: | 20240325 |
| مُعرف محوري في PubMed: | PMC10942386 |
| DOI: | 10.1101/2024.03.01.583044 |
| PMID: | 38496448 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.03.01.583044 |
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