CONSEQUENCES OF ADDITIONAL REALISM: A THREE-DIMENSIONAL COMPUTATIONAL MODEL OF MONOCLONAL CONVERSION IN THE COLONIC CRYPT

Abstract

Colorectal cancer occurs as a result of a sequence of mutations that cause carcinomas to form in the intestine. Due to cell proliferation, migration, and differentiation in the crypts of the surface epithelium of the intestinal tract, this tissue is rapidly renewing and thus a major target for the development of cancer. An understanding of the basic biology and dynamics of the intestinal crypts is necessary in order to gain a deeper understanding of the early development of cancer. Many mathematical models of the crypts of the colon have been considered, but none currently examine the biological and mechanical effects of modeling the crypt in three dimensions. In this study, the consequences of additional realism in the geometry of the murine colon crypt are considered in a spatial model. The results of these simulations show that cells that are farther towards the base of the crypt have an advantage over proliferative cells that are higher up in the crypt, indicating that there is a stem cell niche in which cells have a higher probability of persisting long-term. By comparing these results to existing two-dimensional models, it is also apparent that the additional realism of the three-dimensional crypt geometry generally decreases the time it takes for the clone to dominate the crypt.