Abstract
Recent advance of sequencing technology has revealed genetic alterations in colorectal cancer (CRC). The biological function of recurrently mutated genes has been intensively investigated through mouse genetic models and CRC cell lines. Although these experimental models may not fully reflect biological traits of human intestinal epithelium, they provided insights into the understanding of intestinal stem cell self-renewal, leading to the development of novel human intestinal organoid culture system. Intestinal organoid culture enabled to expand normal or tumor epithelial cells in vitro retaining their stem cell self-renewal and multiple differentiation. Gene manipulation of these cultured cells may provide an attractive tool for investigating genetic events involved in colorectal carcinogenesis.
Highlights
Despite recent advances in therapeutics, colorectal cancer (CRC) is a major health issue; more than a million people develop CRC, causing more than 700 thousand deaths worldwide yearly (Lozano et al, 2012)
Investigators have attempted to identify or isolate colorectal cancer stem cell (CSC); direct evidence of colorectal CSCs has been lacking to date (Clevers, 2011)
Because tissue stem cells were thought to be relatively dormant to evade DNA damage or telomere shortening during DNA replication, these findings led later investigators to assume that +4 position “label-retaining cells” were the intestinal stem cells (ISCs)
Summary
The biological function of recurrently mutated genes has been intensively investigated through mouse genetic models and CRC cell lines. These experimental models may not fully reflect biological traits of human intestinal epithelium, they provided insights into the understanding of intestinal stem cell self-renewal, leading to the development of novel human intestinal organoid culture system. Intestinal organoid culture enabled to expand normal or tumor epithelial cells in vitro retaining their stem cell selfrenewal and multiple differentiation. Gene manipulation of these cultured cells may provide an attractive tool for investigating genetic events involved in colorectal carcinogenesis
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