Inflammatory events during murine squamous cell carcinoma development

Abstract

BackgroundSquamous 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.MethodsWe 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.ResultsELA 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.ConclusionOur results indicate an imbalance of inflammatory mediators in precancerous SCC caused by neutrophils and macrophages and culminating in pro-tumour local tissue alterations.

Inflammasome Activation Is Critical to the Protective Immune Response during Chemically Induced Squamous Cell Carcinoma

“…In order to determine whether the tumor-associate neutrophils (TAN) influenced the MPO and ELA activity, which are mediators associated with SCC development [33] , we analyzed for the presence of these enzymes in the tumor microenvironment. At 12 weeks, we detected higher activity of MPO in the lesions from WT mice than KO groups and no differences related to ELA were observed among the groups ( Fig.…”

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

“…IL-17-producing cells are widely detected and could play a significant role in skin cancers [7,[10][11][12]. For example, several reports suggested the significance of IL-17 signaling in keratinocytes in the tumor formation of cutaneous squamous cell carcinoma [10][11][12].…”

PAD2 Overexpression in Transgenic Mice Promotes Spontaneous Skin Neoplasia

“…A number of mouse models, including models of advanced SCC, have documented a role for inflammation in cancer progression (36). In humans, the links between inflammation and cancer are now so strong that inflammation is considered to be the seventh hallmark of cancer (36,37).…”

“…In humans, the links between inflammation and cancer are now so strong that inflammation is considered to be the seventh hallmark of cancer (36,37). Two key mediators of inflammation-driven cancers are the cytokines, IL6 and IL8, which promote cancer progression by stimulating tumor growth and angiogenesis (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48).…”