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.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)