Tracheal epithelial cell transformation: a model system for studies on neoplastic progression

Abstract

Most in vitro transformation studies have been conducted with fibroblast cultures of various origins. The phenotypic changes known to accompany transformation are therefore primarily those that are typical for transformed fibroblasts. Little information exists concerning phenotypic changes occurring during transformation of epithelial cells in vitro. However, recently a number of transformation studies have been reported with tracheal epithelium as a prototype for epithelium from the conducting airways. The initial studies were carried out with organ culture-cell culture systems. These studies reported the qualitative phenotypic changes developing in primary outgrowth cultures after exposure to the direct acting carcinogen N-methyl-N'-nitrosoguanidine. The phenotypic changes observed are all related to changes of in vitro growth characteristics. Several stages can be observed as the cell cultures progress from a "carcinogen altered" to the neoplastic state. While these studies laid the groundwork for the epithelial transformation field, they did not permit quantitation of transformants, since the size of the exposed cell population is unknown. More recently transformation systems with dispersed primary tracheal epithelial cells have been developed which allow quantitation of transformed phenotypes. These systems are being used for clonal analysis of the process of epithelial cell transformation and to study progression and promotion during development of neoplastic transformation.