Normal Crypt Dynamics
Over 95% of colorectal cancers originate from the surface epithelum. This epithelium renews itself every 4-6 days by a coordinated series of cell proliferation, migration and differentiation events that initiates in the crypts of Lieberkühn (Figure 2). At the bottom of the crypt, a small population of stem cells is believed to divide continuously, producing transit cells.
These semi-differentiated cells divide a several times before undergoing terminal differentiation. At the same time as new cells are being added to the lower third of the crypt, the entire population of semi- and terminally-differentiated cells migrates towards the luminal orifice where terminally differentiated cells are removed from the luminal surface. Along the crypt axis there is thus a clear proliferative hierarchy. The behaviour of each cell is determined by position-specific extracellular signals (e.g. composition of the basal lamina and concentration of Wnt factors) and intracellular gene expression levels.
Figure 2: Normal crypt dynamics. Near the bottom the crypt, stem cells divide asymmetrically, giving one stem cell and one transit cell. Transit cells have the ability to divide rapidly a limited number of times, after which they undergo terminal differentiation. As each stem cell produces a large number of transit and differentiated cells, slight changes in the number of stem cells have important implications for the maintenance of the integrity of the crypt. Fully differentiated cells are removed from the luminal surface by programmed cell death (apoptosis).