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Stem Cell Origin of Cell Lineages, Proliferative Units, and Cancer in the Gastrointestinal Tract

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Stem Cells Handbook

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Abstract

The gastrointestinal (GI) stem cell has the ability to differentiate into every epithelial lineage in the GI tract and is proposed as the target of GI carcinogenesis. There is considerable difference in the epithelial tissue of the GI tract including the oral cavity, pharynx, esophagus, stomach, small intestine, and colon, yet each appears to have a common stem cell that can give rise to both metaplasia and cancer throughout the GI tract. These cells may be located in the basal layer of the mucosa or in specialized niches at the base or just above the base of glands in the stomach and intestines. The underlying mesenchymal cells of the lamina propria provide an environment, that is responsible for normal differentiation. The crypts are composed of monoclonal units of differentiating cells similar to the epidermal poliferative unit of the skin. However, although the crypts are monoclonal, the villi of the small intestine are polyclonal, indicating that multiple crypts may contribute to the cells of the villi. Bone marrow transplantation studies indicate that marrow stem cells can engraft into the small intestine and colon and differentiate into intestinal subepithelial myofibroblast cells located within the lamina propria. Mucosal stem cells may also derive from transplanted bone marrow cells. There is evidence for both monoclonal and polyclonal origins of epithelial cancer. The presence of multiple, synchronous premalignant foci associated with invasive cancer has led to the field cancerization hypothesis, which predicts that a carcinogenic stimulus leads to transformation of multiple cells in a tissue and that one of these “clones” may grow out because of a mutation that favors its expansion over the others. In this case, a polyclonal expansion may be followed by a clonal proliferation, indicating that the carcinogenic process starts out polyclonal and ends up clonal. The “adenomas” of familial adenomatous polyposis and some animal models of carcinogenesis are multiclonal, whereas the cancers in this condition are monoclonal. Even though the clonal nature of the normal expansion of GI cells is well established, the clonal origin of intestinal epithelial neoplasms is unresolved; data support both possibilities. The genetic and molecular regulatory mechanisms involved in GI tumorigenesis are being unraveled, and it may well be that different molecular mechanisms lead to cellular pathways to cancer. For example, a mutation in APC may lead to polyclonal adenoma formation and further mutations to monoclonal expansion.

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Authors
  1. Mairi Brittan BSc
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  2. Nicholas A. Wright MD, PhD
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  1. Wadsworth Center and Ordway Research Institute, Empire State Plaza, Albany, NY, USA

    Stewart Sell MD

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Brittan, M., Wright, N.A. (2004). Stem Cell Origin of Cell Lineages, Proliferative Units, and Cancer in the Gastrointestinal Tract. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_30

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  • DOI: https://doi.org/10.1007/978-1-59259-411-5_30

  • Publisher Name: Humana Press, Totowa, NJ

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