Eosinophils, tissue eosinophilia, and eosinophil-derived transforming growth factor alpha in hamster oral carcinogenesis.

Eosinophilia in tissues and/or circulating blood is known to be associated with a wide variety of malignancies but the role of the eosinophil in neoplastic conditions is not known. Using the cheek pouch of the Syrian hamster as an experimental model for oral carcinogenesis, it has recently been shown that eosinophils at sites of developing oral cancer express the multifunctional cytokine, transforming growth factor alpha (TGF-alpha). This study investigated the time course of eosinophil infiltration, tissue eosinophilia associated with malignant epithelium, and eosinophil-derived TGF-alpha mRNA during the 16-week 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral cancer development process. The results reveal that the occasional eosinophil is normally present in the lamina propria of hamster oral mucosa. With progressive DMBA treatments, there is an increase of eosinophils infiltrating into the lamina propria. By weeks 12-16, the number of eosinophils is significantly higher in DMBA-treated pouches than in control pouches treated with the vehicle mineral oil alone. Analysis of the infiltrating eosinophils into fully developed hamster oral carcinomas reveals that tissue eosinophilia is associated with 78% of the stromal areas associated with malignant epithelium, while only 7% of sites associated with non-tumor oral epithelium (normal, hyperplastic-dysplastic) exhibited eosinophilia. Furthermore, the majority of the eosinophils associated with malignant epithelium were found to contain TGF-alpha mRNA. The number of TGF-alpha mRNAs containing eosinophils associated with malignant oral epithelium is significantly higher than that associated with nonmalignant oral epithelium. Together, these results suggest that eosinophils are recruited to tumor-developing sites, that they predominantly associate with malignant epithelium, and that most tumor-associated eosinophils express the cytokine TGF-alpha.