Roger R. Reddel

Cellular and Molecular Studies of Growth, Differentiation and Neoplastic Transformation of Human Bronchial Epithelial Cells in Vitro

Normal human cells in vitro appear to retain many normal phenotypic properties, remain diploid, eventually undergo senescence and rarely, if ever “spontaneously” transform to malignant cells. Retained properties may include synthesis of classes of proteins associated with specific cell types such as collagens, keratins, or melanin; responsiveness to hormones; and antigenic specificity. In addition, human cells with abnormal phenotypes such as either enzymatic deficits or malignant properties frequently maintain these phenotype in vitro. Human cells cultured in vitro have thus proven to be extremely useful to scientists studying the molecular and biochemical aspects of human carcinogenesis. Such studies have been facilitated by the recent development of improved methods for culturing normal human epithelial tissues and cells1. Chemically defined media have been developed for culturing many of these tissues and cells from normal organs, including those with a high rate of cancer in humans. Serum-free media have several advantages in studies of cultured human cells, including: (a) less experimental variability compared to serum-containing media; (b) selective growth conditions for normal cells of different types (e.g. epithelial versus fibroblastic) or for normal versus malignant cells; (c) ease of identification of growth factors, inhibitors of growth, and inducers of differentiation; and (d) ease of isolating and analyzing secreted cellular products. Advances in cell biology, including the delineation of biochemical and morphological markers of specific cell types, have also facilitated the identification of cells in vitro (including keratins as markers for epithelial cells and collagen types I and III for identifying fibroblasts). These advances have created experimental approaches to answering critical questions in human cell carcinogenesis1,2.