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World J Gastroenterol. Feb 28, 2014; 20(8): 1898-1909
Published online Feb 28, 2014. doi: 10.3748/wjg.v20.i8.1898
Intestinal stem cells and the colorectal cancer microenvironment
Bryan A Ong, Kenneth J Vega, Courtney W Houchen
Bryan A Ong, Kenneth J Vega, Courtney W Houchen, Department of Digestive Diseases, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
Author contributions: Ong BA contributed to literature research, article design, writing, revision, and illustration; Vega KJ contributed to article revision; Houchen CW contributed to article revision; all authors approved the version to be published.
Correspondence to: Courtney W Houchen, MD, Department of Digestive Diseases, University of Oklahoma Health Sciences Center, 1100 N Lindsay Ave, Oklahoma City, OK 73104, United States. courtney-houchen@ouhsc.edu
Telephone: +1-405-2715428 Fax: +1-405-2715803
Received: October 10, 2013
Revised: December 3, 2013
Accepted: January 3, 2014
Published online: February 28, 2014
Abstract

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: Colon cancer stem cells, DCLK1 protein, Stem cell niche, Cell dedifferentiation

Core tip: Colorectal (CRC) cancer stem cells are a theorized but poorly characterized cell population believed to be crucial for tumor growth, spread, and tenacity. CRC stem cells share many similar characteristics of normal intestinal stem cells and are hypothesized to originate directly from them. It appears, however, that both the regulation of normal intestinal stem cells and the development of CRC are far more complex than previously imagined. Likely pivotal to the success of both are plasticity pathways able to reverse cellular fate, and stem cell niche signals, ultimately leading to self-replenishment and sometimes also unwanted dissemination.