Abstract
We present the development and validation of a mathematical model that predicts how glucose dynamics influence metabolism and therefore tumor cell growth. Glucose, the starting material for glycolysis, has a fundamental influence on tumor cell growth. We employed time-resolved microscopy to track the temporal change of the number of live and dead tumor cells under different initial glucose concentrations and seeding densities. We then constructed a family of mathematical models (where cell death was accounted for differently in each member of the family) to describe overall tumor cell growth in response to the initial glucose and confluence conditions. The Akaikie Information Criteria was then employed to identify the most parsimonious model. The selected model was then trained on 75% of the data to calibrate the system and identify trends in model parameters as a function of initial glucose concentration and confluence. The calibrated parameters were applied to the remaining 25% of the data to predict the temporal dynamics given the known initial glucose concentration and confluence, and tested against the corresponding experimental measurements. With the selected model, we achieved an accuracy (defined as the fraction of measured data that fell within the 95% confidence intervals of the predicted growth curves) of 77.2 ± 6.3% and 87.2 ± 5.1% for live BT-474 and MDA-MB-231 cells, respectively.
Highlights
The major source of energy for many cancer cells comes from a high rate of glycolysis followed by lactate fermentation in the cytosol, even in the presence of sufficient oxygen—a phenomenon known as the Warburg effect [1, 2]
The average number of live cells for each experiment at the end of day 4 was significantly different among the groups with different initial conditions (p < 10−5)
We have developed and validated an experimental-mathematical approach that is capable of accurately predicting how glucose availability influences tumor cell proliferation
Summary
The major source of energy for many cancer cells comes from a high rate of glycolysis followed by lactate fermentation in the cytosol, even in the presence of sufficient oxygen—a phenomenon known as the Warburg effect [1, 2]. This contrasts with normal cells that exhibit a comparatively low rate of glycolysis followed by oxidative phosphorylation in the mitochondria. Figshare.14544462.v1 3) The code for the MDAMB-231 data is located here: https://doi.org/10.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
