Modelling the flow [corrected] cytometric data obtained from unperturbed human tumour cell lines: parameter fitting and comparison.
In this paper we firstly present three alternative formulations of a mathematical model for human tumour cell lines unperturbed by cancer therapy. The model counts the number density of cells in each phase of the cell cycle over time where cells are differentiated by their DNA content. Data are available from the Auckland Cancer Society Research Centre, Auckland, New Zealand, in the form of DNA histograms or profiles from 11 different human tumour cell lines (i.e. in vitro) unperturbed by cancer therapy. We then apply one (computationally fast) formulation of the model and discover that although in general different combinations of parameter values give rise to very different DNA profiles it is possible that different combinations of parameter values give rise to virtually identical profiles. Experimental estimates of the rate of transition from the G1-phase (growth) to the S-phase (DNA synthesis) enable us to uniquely determine other model parameters of interest that give the least square error between the model and data. We finally apply our model to each of the 11 different cell lines and compare cell cycle phase transit times. Although the DNA histograms of each of the cell lines have similar shapes these cell lines have different combinations of transit times to each other, which could explain why they often react very differently when exposed to anti-cancer therapies during laboratory experiments. An understanding of the in vitro situation may give an insight into why some human cancer patients do not respond to cancer therapy.
Basse
Britta
B
Max Planck Institute for Mathematics in the Sciences, Inselstrasse 22-26, 04103 Leipzig, Germany. basse@mis.mpg.de
Baguley
Bruce C
BC
Marshall
Elaine S
ES
Wake
Graeme C
GC
Wall
David J N
DJ
D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*
D004273:DNA, Neoplasm