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

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