Interdependent Regulation of Epithelial Cell Replication by Nutrients, Hormones, Growth Factors, and Cell Density

Considerable progress in human epithelial cell culture procedures has permitted defining nutritional growth requirements in low-serum or serum-free conditions for normal and tumorigenic prostatic and bronchial epithelial cells. Assay conditions revealed interrelationships between cell density and nutrient and factor requirements for both growth enhancement and terminal differentiation. Interactions among nutrients, growth factors, and serum have been delineated by applying the principles of Michaelis-Menton kinetics to clonal growth data: 1) epidermal growth factor (EGF) reduced the half-maximal requirement for serum and Ca2+, but neither serum nor Ca2+ altered the EGF requirement; 2) serum stimulated terminal differentiation of bronchial epithelial cells and EGF; cholera toxin and growth-arrested Swiss mouse 3T3 feeder cells inhibited serum-induced differentiation; 3) differences in the interaction of Ca2+- and Mg2+-dependent growth control of prostatic and bronchial epithelial cells were noted; and 4) a phenotypic reduction in nutritional growth requirements for bronchial epithelial cells was obtained by supplementing serum-free medium with triiodothyronine. These results indicate significant differences in both nutritional requirements and interactions for different types of human epithelial cells. Elucidation of these differences may point to plausable reasons why the malignant transformation potential of tissue types varies with specific carcinogens.