Intestinal stem cells and the colorectal cancer microenvironment

World J Gastroenterol. 2014 Feb 28;20(8):1898-909. doi: 10.3748/wjg.v20.i8.1898.


Colorectal cancer (CRC) remains a highly fatal condition in part due to its resilience to treatment and its propensity to spread beyond the site of primary occurrence. One possible avenue for cancer to escape eradication is via stem-like cancer cells that, through phenotypic heterogeneity, are more resilient than other tumor constituents and are key contributors to cancer growth and metastasis. These proliferative tumor cells are theorized to possess many properties akin to normal intestinal stem cells. Not only do these CRC "stem" cells demonstrate similar restorative ability, they also share many cell pathways and surface markers in common, as well as respond to the same key niche stimuli. With the improvement of techniques for epithelial stem cell identification, our understanding of CRC behavior is also evolving. Emerging evidence about cellular plasticity and epithelial mesenchymal transition are shedding light onto metastatic CRC processes and are also challenging fundamental concepts about unidirectional epithelial proliferation. This review aims to reappraise evidence supporting the existence and behavior of CRC stem cells, their relationship to normal stem cells, and their possible dependence on the stem cell niche.

Keywords: Cell dedifferentiation; Colon cancer stem cells; DCLK1 protein; Stem cell niche.

Publication types

  • Review

MeSH terms

  • Cell Differentiation
  • Cell Proliferation
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Intestines / cytology*
  • Myofibroblasts / metabolism
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / cytology*
  • Paneth Cells / cytology
  • Phenotype
  • Signal Transduction
  • Stem Cell Niche
  • Surface Properties
  • Tumor Microenvironment*