Increased fibroblast density in actinic cheilitis: association with tryptase-positive mast cells, actinic elastosis and epithelial p53 and COX-2 expression.

BACKGROUND: Actinic cheilitis (AC) is characterized by epithelial and connective tissue alterations caused by ultraviolet sunlight overexposure known as photodamage. Fibroblasts have been linked to photodamage and tumor progression during skin carcinogenesis; however, their role in early lip carcinogenesis remains unknown. The aim of this study was to assess the density of fibroblasts in AC and normal lip (NL) samples and determine their association with markers of lip photodamage. METHODS: Fibroblasts, mast cells, p53, COX-2, and elastin were detected in NL (n = 20) and AC (n = 28) biopsies using immunohistochemistry/histochemistry. Mast cell and fibroblast density and epithelial p53 and COX-2 expression scores were then obtained. Elastosis was scored 1-4 according to elastin fiber density and tortuosity. RESULTS: Fibroblasts, mast cells, p53, COX-2, and elastosis were increased in AC as compared to NL (P < 0.001). Multivariate analysis showed an association between fibroblast and mast cell density at the papillary and reticular areas of AC and NL (P < 0.05). Papillary fibroblast density was also associated with epithelial p53 and COX-2 expression (P < 0.05). Increased fibroblast density, both papillary and reticular, was found in the high elastosis group (scores 3-4) as compared to the low elastosis group (scores 1-2) (P < 0.01). Increased reticular mast cell density was detected only in the high elastosis group (P < 0.01). CONCLUSIONS: Fibroblasts are increased in AC, and they are associated with mast cell density, epithelial p53 and COX-2 expression, and actinic elastosis. Therefore, fibroblasts may contribute to lip photodamage and could be considered useful markers of early lip carcinogenesis.

The influence of mast cell mediators on migration of SW756 cervical carcinoma cells.

The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and Win 55,212-2. Therefore, the specific effects of histamine and cannabinoids on SW756 migration and LAD2 activation were analyzed. Histamine added to the in vitro assay of scratch wound healing either increased or inhibited SW756 migration rate by acting either on H1R or H4R, respectively. Cannabinoids acted on CB1 receptors to inhibit SW756 migration. Supernatants from SW756 cells stimulated LAD2 cell degranulation, which in turn was inhibited by cannabinoids acting via CB2 receptors. RT-PCR showed that SW756 expressed mRNA for CB1, CB2, H1R, H2R, and H4R. On the other hand, LAD2 expressed mRNA for all four HRs and CB2. The results suggest that mast cells could be contributing to cervical cancer cell invasion and spreading by the release of histamine and cannabinoids. Therefore, therapeutic modulation of specific mast cell mediators may be beneficial for cervical cancer treatment.