"The initial engraftment of tumor cells is critical for the future growth pattern"
Xenograft mouse models are used to study mechanisms of tumor growth and metastasis formation as well as investigating the efficacy of different therapeutic interventions. After injection the engrafted cells form a local tumor nodule whose size can be measured repeatedly during an experiment. The so obtained experimental growth data can be described mathematically by suitable growth functions, the choice of which is not always obvious. By applying nonlinear curve fitting, growth parameters can be determined that provide information on the tumor growth.
We used self-generated synthetic data including random measurement errors to research the accuracy of parameter estimation based on caliper-measured experimental tumor data. Fit metrics were investigated to identify the most appropriate growth function for a given synthetic dataset. For curve fitting with fixed initial tumor volume, we varied the fixed initial tumor volume during curve fitting to investigate the effect on the resulting estimated parameters. To determine the number of tumor cells that survive initially after injection into mice, we performed ex vivo bioluminescence imaging of the tumor nodules on day 1, 2, 4 and 8 after injection. By this experimental approach we determined the effect of incorrect assumed initial tumor volume in experiments.
An incorrect assumed value of the initial tumor volume during the parameter estimation process leads to large deviations in the resulting growth parameters. Therefore, the actual number of cancer cells engrafting directly after subcutaneous injection is critical for future tumor growth and distinctly influences the parameters for tumor growth by curve fitting.
Hoffmann, B., Lange, T., Labitzky, V., Riecken, K., Wree, A., Schumacher, U., Wedemann, G. The initial engraftment of tumor cells is critical for the future growth pattern: a mathematical study based on simulations and animal experiments. BMC Cancer 20, 524 (2020). https://doi.org/10.1186/s12885-020-07015-9