Modification by serum of differentiation of cultured human myeloid leukemia cells in response to 12-O-tetradecanoylphorbol-13-acetate.

In medium with serum, 12-O-tetradecanoylphorbol-13-acetate (TPA) induced alpha-naphthyl acetate esterase activity in human promyelocytic leukemia cells (HL-60), adherence of the cells to the culture dish, and their change into forms that were morphologically similar to macrophages. HL-60 cells grew in the absence of serum in synthetic medium supplemented with insulin, transferrin, and several trace elements, and could be maintained for more than 6 months in this medium. Induction of differentiation by TPA was observed with cells grown in serum-free medium. Human myeloid leukemia cells (K562-4) cultured in medium with serum could not be induced to differentiate even in the presence of TPA, but their differentiation into macrophages in the presence of TPA, arginase or actinomycin D was observed after they had been grown in serum-free medium for 4 months. Addition of serum inhibited the induction of differentiation of HL-60 and K562-4 cells that had been grown in serum-free medium. Calf serum was more inhibitory than fetal calf serum on TPA-induced differentiation, but there was no significant difference in the effects of the two sera on induction by actinomycin D or arginase. These results suggest that the different responses in media with different sera may be specific to TPA. Induction of adhesiveness of K562-4 cells by TPA required some unknown serum factor(s), although addition of serum inhibited the inductions of morphological and functional differentiation. The relation between the ability of K-562-4 cells to be induced to differentiate into macrophages and long-term cultivation in serum-free medium is discussed.