Formation, growth and morphology of multicellular tumor spheroids from a human colon carcinoma cell line (LoVo).

LoVo human colon carcinoma cells cultured by a liquid overlay technique form and grow as multicellular tumor spheroids. The growth curve of LoVo spheroids exhibits Gompertzian growth kinetics, i.e., exponential growth for 10 days, followed by exponential retardation in the rate of growth. Doubling time in the exponential growth phase is longer than in monolayer cultures (5 days for LoVo spheroids vs. 37 h for monolayers). When LoVo spheroids reach a diameter of about 300 microns, a necrotic core appears in their center and continuously increases with spheroid growth. The cell ultrastructure and organization in spheroids closely resemble those of the same cells when grown as tumors in vivo or as monolayer, i.e. intestinal epithelium, desmosomes, intracytoplasmic lumina and acinar structures. Individual cells from spheroids can be obtained by trypsinization and assayed for colony formation. LoVo spheroids provide a model which can be readily manipulated and appears to be suitable for evaluation of anticancer drugs. A comparison of LoVo spheroids exposed to doxorubicin with the same cells grown in monolayers emphasized the role of cell organization in determining drug resistance.