Chemically induced skin carcinogenesis: Updates in experimental models (Review) - PubMed (original) (raw)

Review

Chemically induced skin carcinogenesis: Updates in experimental models (Review)

Monica Neagu et al. Oncol Rep. 2016 May.

Abstract

Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology.

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Figures

Figure 1

Figure 1

The cascade of acute and chronic skin inflammation. (A) The initial skin injury triggers intravascular processes that promote neutrophil adhesion and transmigration. Resident macrophages and mastocytes release pro-inflammatory factors and chemoattractants; (B) lymphocytes and monocytes have enhanced adhesion capacities and further transmigrate into the extravascular space. Transmigrated cells and resident macrophages secrete pro-inflammatory factors and chemoattractants, stimulating collagen production and perpetuating the inflammatory response (copyright from ref. 29).

Figure 2

Figure 2

Elements of acute and chronic inflammation that are linked to tumorigenesis. (A) T and B lymphocytes secrete factors that induce the M1 macrophage phenotype, promote the innate immune response, promote cytotoxic T lymphocyte (CTL)-mediated destruction, enhance the antigen-presenting capacity and increase natural killer (NK) cell activity. All these processes have a potent antitumorigenic effect; (B) T and B lymphocytes secrete factors that induce the M2 macrophage phenotype, enhance myeloid suppressor activity, reduce CTL activity, decrease the antigen-presenting capacity and increase NK cell activity. All these processes have a potent pro-tumorigenic effect (copyright from ref. 29). IL, interleukin; IFN-γ, interferon-γ; TGF-β, ransforming growth factor β; Ig, immunoglobulin.

Figure 3

Figure 3

Reflectance confocal microscopy (RCM) and histopathological images of chemically induced skin tumors in C57BL/6 mice. (A) RCM mosaic showing a tumoral structure with an irregular architecture; (B and C) details of RCM image showing bright fiber-like structures (white arrowhead), large cells with dark nuclei (white arrows) and numerous small hyper-refractile structures (white asterisk); (D) poorly differentiated carcinoma expressing neuron-specific enolase, week cytokeratin expression, negative melanocyte markers (hematoxylin and eosin staining, original magnification, ×100); (E an F) histological details (hematoxylin and eosin staining, original magnification, ×400).

Figure 4

Figure 4

(a) Reflectance confocal microscopy (RCM) mosaic showing a tumoral structure with a multilobular architecture; (B) details of RCM image showing atypical cells (white asterisk) and blood vessels (red arrow); (C) cutaneous papillomas presenting intra-epithelial keratinocytes neoplasia I/II (hematoxylin and eosin staining, original magnification, ×100); (D) histological detail (hematoxylin and eosin staining, original magnification, ×400).

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