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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Journal of Inflammation 1/2012

Inflammatory events during murine squamous cell carcinoma development

Zeitschrift:
Journal of Inflammation > Ausgabe 1/2012
Autoren:
Thais Helena Gasparoto, Carine Ervolino de Oliveira, Luisa Thomazini de Freitas, Claudia Ramos Pinheiro, Rodrigo Nalio Ramos, André Luis da Silva, Gustavo Pompermaier Garlet, João Santana da Silva, Ana Paula Campanelli
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-9255-9-46) contains supplementary material, which is available to authorized users.

Competing interests

Authors declare no conflict of interest.

Authors’ contributions

THG had the overall responsibilities of the experiment design and statistical analysis, the concept and wrote the manuscript. CdO carried out chemical induction of squamous cell carcinoma, histological experiments and counting of inflammatory infiltration in the lesions. LTdF carried out chemical induction of squamous cell carcinoma and counting of inflammatory infiltration in the lesions. CRP and RNR carried out chemical induction of squamous cell carcinoma. ALdScarried out histological experiments and counting of inflammatory infiltration in the lesions. GPG, JSdS and APC had shared the concept and supported the manuscript. APC had overall responsibilities of fund management, experimental design and wrote the manuscript. All the authors have read and approved the final manuscript.

Abstract

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Literatur
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