Inflammatory Events During Murine Squamous Cell Carcinoma Development
Open accessAbstract
BACKGROUND: Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. In SCC, tumour development is accompanied by an immune response that leads to massive tumour infiltration by inflammatory cells, and consequently, local and systemic production of cytokines, chemokines and other mediators. Studies in both humans and animal models indicate that imbalances in these inflammatory mediators are associated with cancer development. METHODS: We used a multistage model of SCC to examine the involvement of elastase (ELA), myeloperoxidase (MPO), nitric oxide (NO), cytokines (IL-6, IL-10, IL-13, IL-17, TGF-β and TNF-α), and neutrophils and macrophages in tumour development. ELA and MPO activity and NO, IL-10, IL -17, TNF-α and TGF-β levels were increased in the precancerous microenvironment. RESULTS: ELA and MPO activity and NO, IL-10, IL -17, TNF-α and TGF-β levels were increased in the precancerous microenvironment. Significantly higher levels of IL-6 and lower levels of IL-10 were detected at 4 weeks following 7,12-Dimethylbenz(a)anthracene (DMBA) treatment. Similar levels of IL-13 were detected in the precancerous microenvironment compared with control tissue. We identified significant increases in the number of GR-1+ neutrophils and F4/80+/GR-1- infiltrating cells in tissues at 4 and 8 weeks following treatment and a higher percentage of tumour-associated macrophages (TAM) expressing both GR-1 and F4/80, an activated phenotype, at 16 weeks. We found a significant correlation between levels of IL-10, IL-17, ELA, and activated TAMs and the lesions. Additionally, neutrophil infiltrate was positively correlated with MPO and NO levels in the lesions. CONCLUSION: Our results indicate an imbalance of inflammatory mediators in precancerous SCC caused by neutrophils and macrophages and culminating in pro-tumour local tissue alterations.
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The MPO system has been involved in various skin pathologies, either serving as a causative factor or biomarker in inflammation, contact hypersensitivity and irritation, psoriasis, UV-damage, photoaging, and carcinogenesis.
“beyond a role in cutaneous innate immunity, the MPO system has also been involved in various skin pathologies, either serving as a causative factor or biomarker in inflammation, contact hypersensitivity and irritation, psoriasis, UV-damage, photoaging, and carcinogenesis (51–59).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [55]
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Case series: Rapidly growing squamous cell carcinoma after cutaneous surgical intervention
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An Examination and Categorical Analysis of Squamous Cell Carcinoma
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- Authors
- Gasparoto, T. H., de Oliveira, C. E., de Freitas, L. T., Pinheiro, C. R., Ramos, R. N., da Silva, A. L., Garlet, G. P., da Silva, J. S., & Campanelli, A. P.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Campanelli, Ana Paula
- Venue
- Journal of Inflammation
- Published
- 2012-11-23
- Volume
- 9
- Issue
- 1
- Pages
- 46-46
- ISSN
- 1476-9255 (ISSN-L)
- PMC
- PMC3542019
- OpenAlex
- W2021380609
- Cited by
- 35
- References
- 76
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 2
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Inflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (publishedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (11/03195-1)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- squamous cell carcinoma, tumor inflammation, precancerous lesions, neutrophils, tumour-associated macrophages, myeloperoxidase, elastase, nitric oxide, cytokines, IL-10, IL-17, TNF-α, TGF-beta, interleukin-6, IL-13, DMBA-induced carcinogenesis, Gr-1, F4/80, tumor microenvironment
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