Tissue normalizing capacity as a key determinant of carcinogenesis: an in silico simulation
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A perturbed microenvironment is at the core of carcinogenesis. Here, we used a 2D cellular automata model to simulate how cancers are generated in epithelial tissue. We applied several mathematical rules to simulate tissue renewal and surrounding cell control. Under the simulation, we showed that the average value of surrounding normal cells could be an indicator for the tissue normalizing capacity (TNC). Further, we found the incidence of carcinogenesis correlated inversely with the TNC. Interestingly, we also found that multi-round mutagenesis could gradually disturb the TNC when compared to one-round mutagenesis: cancer incidence increased significantly compared to one-round mutagenesis. Our model suggests that the genetic alterations (mutations) by themselves were not sufficient to initiate cancer. The perturbation of TNC could be a key process leading to carcinogenesis.
KeywordsCarcinogenesis Epithelial cancers In silico simulation Somatic mutation theory Tissue normalization Tissue organization field theory
I thank Prof. Stuart G Baker, from Biometry Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, USA, for the critical review of the manuscript. I also thank Prof. Carlos Sonnenschein, from Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, USA, for this candid comments and careful revision of the manuscript.
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