Stem cell retrograde: A new reason why colorectal cancer is more common than small intestinal cancer?

Schematic diagram of intestinal structure and stem cell movement in crypts

The intestine is exposed to a dynamic internal environment that is full of physiological stimuli and has a high risk of being invaded by pathogenic factors. It has dynamic fold units referred to as crypts that are composed of epithelial cells to ward off potential damage from gut lumen. Apart from the crypt, the small intestine (SI) contains villi that is covered by functionally differentiated cells, such as absorptive epithelial cells to maintain nutrient exchange with luminal environments. Intestinal stem cells (ISCs) are responsible for self-repair mechanisms of the intestine epithelium. They have the ability to differentiate and proliferate, are well protected, and are located at the bottom of the intestinal crypt structure. This regenerative mechanism allows stem cells to differentiate and replenish the epithelial cell population to cover the entire gut. Morphologically, the SIs have villi, while the large intestines do not. In addition to this distinction, Azkanaz et al. showed that SI stem cells have a strong retrograde phenomenon, while large intestine stem cells exhibit a weak retrograde phenomenon.