| Abstract | A disruption of epithelial morphogenesis is thought to be involved in the initiation of cancer, however, little is known about the cell biology of early neoplastic lesions. Computational models can facilitate in the study of early cancer lesions by directing essential empirical data collection and by integrating results in quantitative outcomes. Here, we present IBCell, a computational model of epithelial acinar structures that predicts the disruptive effects of altered cell-microenvironment interactions on epithelial morphogenesis. A systematic investigation using IBCell reveals a range of model parameters (in terms of cell sensitivity to external cues) for which robust acinar structures form, and the ranges of parameters leading to abnormal geometrical forms resembling tumor-like morphologies, such as: acini with filled lumen or cell clusters with uncontrolled growth. The results obtained from computational simulations are compared (in both, a qualitative and quantitative way) to three-dimensional in vitro experiments on a non-tumorigenic MCF10A cells and some mutants derived from this cell line. |
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