TGF-alpha and oral carcinogenesis.

Abstract

Transforming growth factor-alpha (TGF-alpha) has been shown to be consistently expressed by tumours of epithelial origin, particularly squamous and renal carcinomas. Epithelial tumours are often found to concurrently express the receptor to TGF-alpha, namely epidermal growth factor receptor (EGFR), at elevated levels. The simultaneous expression of TGF-alpha and EGFR by the carcinoma cells is thought to trigger the autocrine growth pathway, resulting in uncontrolled proliferation. Similar observations of elevated TGF-alpha/EGFR expression have been detected in oral squamous carcinomas from human and animal sources. By RNA blotting analyses, elevated levels of TGF-alpha/EGFR expression have been consistently observed with malignant human and hamster oral cancers. Interestingly, by use of cellular localisation techniques of in situ hybridisation and immunohistochemistry, we have shown that there is another, previously unnoticed, cellular source of TGF-alpha at oral tumour sites. Eosinophils are a major cellular source of this growth factor in oral cancer and their presence is tightly associated with malignant oral epithelium. Furthermore, transformed oral epithelium in vivo has been shown to be associated with elevated levels of EGFR expression. Thus quantitative changes in TGF-alpha and EGFR levels in the microenvironment of oral tumours have been observed in vivo. With the hamster oral cancer model, the stage is therefore set to elucidate the cellular and molecular contributions of TGF-alpha and EGFR in the process of oral cancer development.