Stem cells in the context of colon carcinogenesis (a literature review)

Abstract

Aim. To analyze the latest literature data on stem cells in general, intestinal stem cells in particular, as well as cancer stem cells in the context of colon carcinogenesis. Over the past decade, a significant amount of data confirming the existence of cancer stem cells, their importance in cancer progression, resistance to current treatment regimens, and the occurrence of relapses has been accumulated. These cells are a small fraction of cancer cells that initiate tumor growth and provide tumor tissue heterogeneity. In addition, these cells are distinguished by a significant resistance to effects of various cytotoxic factors. Therefore, the possibility of isolating cancer stem cells and further targeted action are highly important for enabling a complete tumor eradication. A study on intestinal stem cells has always been in the focus of stem cell biology researchers’ attention because intestinal stem cells are an example of an active cell population that provides regular rapid renewal of the epithelium, which is constantly exposed to toxic, bacterial, and other aggressive factors. Accordingly, colon carcinogenesis is a convenient model for studying the role of stem cells in tumorigenesis. At the same time, there are two main current schemes of colon carcinogenesis, which are acknowledged – these are so-called “bottom-up” and “top-down” modes of transformed cell spreading. The “bottom-up” scheme was substantiated first, proving to be in good agreement with modern ideas about the structure of intestinal crypts. However, a little later, reports about the possibility of the “top-down” direction began to appear: differentiated cells located in the superficial parts of the intestinal crypts, undergoing mutations, could dedifferentiate and return to the basal parts; a pathological increase in the surface epithelial cells proliferation level was possible as well, leading to an increase in the luminal surface area, formation of grooves mimicking the intestinal crypts. This review provides the latest data on stem cells in general, in particular on intestinal stem cells, as well as on cancer stem cells in the context of colon carcinogenesis. We also analyze the latest literature data on the possibility of isolating cancer stem cells in colon carcinomas using molecular markers, difficulties associated with this process, and issues that are still unresolved. Conclusions. Today, there is no doubt about the existence and importance of cancer stem cells in carcinomas. Quite a lot of molecular markers of cancer stem cells have been identified and studied. It is worth noting that certain aspects of cancer stem cells can not be studied one-sidedly but require a multidimensional analysis.