An agent-based model of anoikis in the colon crypt displays novel emergent behaviour consistent with biological observations

Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth. Model simulations yield previously unseen emergent phenomena, such as localization of cell death to a small region of the crypt mouth which corresponds with that observed in vivo. A mechanism emerges in the model for regulation of crypt cellularity in response to changes in either cell proliferation rates or membrane adhesion strengths. We show that cell shape assumptions influence this behaviour, with cylinders recapitulating biology better than spheres. Potential applications of the model include determination of roles of mutations in neoplasia and exploring factors for altered crypt morphodynamics

A cellular based model of the colon crypt suggests novel effects forApc phenotype in colorectal carcinogenesis

Colorectal cancer (CRC) is a major cause of cancer mortality; loss of the Apc gene is an early step in the formation of CRC. A new computational model of the colonic crypt has been developed to simulate the effects of Apc loss. The model includes a region of flat mucosa, which has not previously been considered in the context of Apc loss. The model suggests that Apc loss confers a survival advantage at the crypt mouth which may be a previously unknown method of mutation fixation