Stem Cells in Colorectal Cancer: New Potential Therapeutic Target

Abstract

Within the crypts of the intestinal mucosa, intestinal epithelium is a permanently renewing tissue, the architecture of which is maintained by the ability of the intestinal stem cells to self-renew and to generate a hierarchy of proliferative and differentiated cells. In the hierarchical structure of intestinal epithelia, the balance between proliferation and cell death is important for homeostasis. This unique structure of intestinal mucosa, crypt axis, is supported by micro-environmental factors, and the disruption of the homeostasis of the crypt axis can develop colorectal neoplasia. Recent evidence suggests that colorectal cancer may arise from mutated colorectal stem or progenitor cells termed colorectal cancer stem cells (CSC) or initiating cells because of their exclusive ability to sustain tumor formation. Colorectal CSC have been identified based on the expression of cell surface markers such as CD133, CD44 and CD166, and these cells have stem/progenitor cell properties, the ability to self-renew, differentiate, and proliferate indefinitely to drive continuous expansion of the malignant cell population. The CSCs, in limited number within the bulk of the tumor, may account for their capability of escaping conventional therapies, thus leading to disease relapse and metastasis. To overcome these malignant features of cancer, the researchers emphasize the importance of better characterizing CSC to target the CSC.