Stem cell relationships and the origin of gastrointestinal cancer

Gastrointestinal stem cells have the capacity for long-term self-replication and the ability to give rise to all other epithelial cell lineages. These properties make them essential since they maintain tissue homeostasis by regulating cell turnover depending on the current demand. However, they are also important players in the earliest stages of gastric and colonic cancer, as they form a target for mutations to accumulate and lead to the development of the malignant phenotype. Due to the lack of reliable markers, gastrointestinal stem cells are difficult to define and characterise. This limits the knowledge about their number and position within the gastric gland and the intestinal crypt, respectively, and consequently about the clonal structure of these units. Therefore, the morphological events of early gastrointestinal carcinoma formation and expansion are hotly debated. In this review we summarize the properties of gastrointestinal stem cells and illuminate their role in the development of the earliest lesions in the gastric and colonic mucosa. We also resume current opinions about the morphological pathways and the clonality of these neoplasias and the subsequent mechanism of spread within the adjacent tissues.