Inflammatory events during murine squamous cell carcinoma development

Autor(es)

Gasparoto, Thais Helena ^[1] ; de Oliveira, Carine Ervolino ^{[1, 2]} ; de Freitas, Luisa Thomazini ^[1] ; Pinheiro, Claudia Ramos ^[1] ; Ramos, Rodrigo Nalio ^[1] ; da Silva, Andre Luis ^[1] ; Garlet, Gustavo Pompermaier ^[1] ; da Silva, Joao Santana ^[3] ; Campanelli, Ana Paula ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci Microbiol & Immunol, Bauru, SP - Brazil

^[2] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol Oral Pathol, Bauru, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inflammation-London; v. 9, NOV 23 2012.
• Citações Web of Science: 9

Resumo

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-beta and TNF-alpha), and neutrophils and macrophages in tumour development. ELA and MPO activity and NO, IL-10, IL-17, TNF-alpha and TGF-beta levels were increased in the precancerous microenvironment. Results: ELA and MPO activity and NO, IL-10, IL-17, TNF-alpha and TGF-beta 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. (AU)

• Processo FAPESP: 11/03195-1 - O papel do inflamassoma nos tumores quimicamente induzidos
• Beneficiário: Ana Paula Campanelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/14127-7 - O papel do inflamassoma nos tumores quimicamente induzidos
• Beneficiário: Thaís Helena Gasparoto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/03471-9 - Modulação da resposta imune durante o desenvolvimento de carcinoma espinocelular
• Beneficiário: Eduardo Bertoli Belai
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 06/01617-8 - Estudo do papel de células T regulatórias no desenvolvimento de carcinoma oral de células escamosas
• Beneficiário: Rodrigo Nalio Ramos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica