Modeling autostimulation of growth in multicellular tumor spheroids.

We report the development of a growth model that includes the positive regulatory feedback by cell-cell interactions. It is based on the model by Wheldon et al. (J Theor Biol, 38 (1973) 627) and Cox et al. (Comput Biomed Res, 13 (1980) 445) and is characterized by biologically interpretable parameters. We applied the model to growth of multicellular spheroids formed by V79 Chinese hamster fibroblasts. The new model resulted in a statistically sound fit. We compared the applicability of our model, of the model by Wheldon et al. and Cox et al. as well as of the related model by Piantadosi (Comput Biomed Res, 18 (1985) 220). We affiliated the models with each other within a nesting scheme and compared their respective fits to data by the F-test. Our model yielded a fit statistically equivalent to the fit by the model of Piantadosi. However, in distinction to other models, the estimated cellular doubling time in our model agreed better with the respective experimentally determined value.