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Mathematical modelling forms a key component of systems biology, offering insights that complement and stimulate experimental studies. In this review, we illustrate the role of theoretical models in elucidating the mechanisms involved in normal intestinal crypt dynamics and colorectal cancer. We discuss a range of modelling approaches, including models that describe cell proliferation, migration, differentiation, crypt fission, genetic instability, APC inactivation and tumour heterogeneity. We focus on the model assumptions, limitations and applications, rather than on the technical details. We also present a new stochastic model for stem-cell dynamics, which predicts that, on average, APC inactivation occurs more quickly in the stem-cell pool in the absence of symmetric cell division. This suggests that natural niche succession may protect stem cells against malignant transformation in the gut. Finally, we explain how we aim to gain further understanding of the crypt system and of colorectal carcinogenesis with the aid of multiscale models that cover all levels of organization from the molecular to the whole organ.

Original publication

DOI

10.1111/j.1365-2184.2006.00378.x

Type

Journal article

Journal

Cell Prolif

Publication Date

06/2006

Volume

39

Pages

157 - 181

Keywords

Cell Differentiation, Cell Movement, Cell Proliferation, Cell Transformation, Neoplastic, Colorectal Neoplasms, DNA Methylation, Gene Expression, Genes, APC, Humans, Models, Theoretical, Subcellular Fractions