Heterogeneity in Colorectal Cancer Stem Cells

Cancer stem cells (CSC) have attracted a great deal of interest for their clinical relevance in a range of cancers, including colorectal cancer. CSCs were initially considered to be cell populations with homogeneous, well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent phenotypically and functionally heterogeneous populations. Recent studies demonstrate colorectal CSCs to be dynamic rather than static, and continuously altered by multiple extrinsic and intrinsic factors. Thus, CSCs no longer should be viewed as a fixed target population, and we should note that their heterogeneous and dynamic nature presents a serious problem for the development and implementation of specific therapeutic strategies. This review summarizes past and current literature related to the heterogeneity and dynamics of colorectal CSC populations, focusing on evidence for distinct subpopulations, and signaling pathways, and intra- and extratumoral factors involved in their regulation in cancer tissues.