Towards a multiscale model of colorectal cancer

Figure 1 Normal colonic mucosa. The normal colonic mucosa consists of crypts (lined with epithelium) embedded within a connective tissue stroma. The mucosa rests on a layer of smooth muscle, called the muscularis mucosae, below, which is a loose connective tissue layer, called the submucosa. The epithelium consists of a number of different cell types including goblet cells (containing mucin), enterocytes and neuroendocrine cells (which secrete hormones). The crypts are enveloped by a sheath of myofibroblasts that are separated from the epithelium by basement membrane. The stroma contains a number of different cell types including macrophages, fibroblasts and lymphoid cells. The crypt is a dynamic structure that turns over every 3-6 d. The base of the crypts contains the stem cells that are thought to give rise to transit amplifying cells. The cells migrate up the crypt and undergo differentiation along the way. The goblet cells secrete mucin into the crypt and intestinal lumen and the surface epithelium usually contains few goblet cells. Upon reaching the surface, the cells undergo apoptosis and are shed into the lumen. The migration along the crypt by the epithelial cells is accompanied by a similar migration of myofibroblasts. The microenvironment is thought to change along the crypt axis and this is thought to give environmental cues for induction of maturation and inhibition of proliferation.