Marker profiling of normal keratinocytes identifies the stroma from squamous cell carcinoma of the oral cavity as a modulatory microenvironment in co-culture

Abstract

PURPOSE: The microenvironment established by stromal cells may or may not influence phenotypic aspects of epithelial cells and may be relevant for tumor and stem cell biology. We address this issue for keratinocytes using tumor-derived stromal cells in a co-culture system. MATERIALS AND METHODS: We isolated stromal cells from human squamous cell carcinoma tissue and studied their effect on phenotypic characteristics of normal human interfollicular keratinocytes in vitro. RESULTS: Stromal fibroblasts significantly influence immuno- and lectin cytochemical properties of co-cultured normal keratinocytes. Expression of keratins 8 and 19, the nucleolar protein nucleostemin, parameters related to adhesion/growth-regulatory galectins and the epithelial-mesenchymal transition were altered. This biological activity of tumor-derived stromal cells, which did not require cell contact, appeared to be stable, because it was maintained during passaging of keratinocytes in the absence of cancer cells. CONCLUSIONS: Tumor-derived stromal fibroblasts acquire distinct properties to shape a microenvironment conducive to altering the phenotypic characteristics of normal epithelial cells in vitro.