Stem cells and their implications for colorectal cancer

The colonic crypt is home to several multipotent stem cells. These stem cells reside in a niche at the base of the crypt, which controls their behavior and maintains the stem cell's homeostasis through a variety of signaling pathways and interactions. Several attempts have been made to define markers that can identify colonic stem cells, the most useful of which is Lgr5, a Wnt target gene. Although the crypt base contains several stem cells, each colonic crypt comprises a single clone of cells. Investigators have attempted to reconcile these apparently contradictory observations by conducting research into stem cell division. The propagation of stem-cell-acquired mutations through a crypt results in a monocryptal adenoma that, through crypt fission, develops into a microadenoma. Some early adenomas become polyclonal through an as yet unknown mechanism. The discovery of subpopulations of cancer cells that can initiate tumors when implanted into mice has renewed interest in the existence of cancer stem cells, especially with regard to their implications for the use of chemotherapy. Various potential markers of cancer stem cells have been investigated, particularly CD133, but the cancer stem cell theory still has some limitations.