Stem cell theory of colorectal cancer and its connection with molecularbiological data

Abstract

Colorectal cancer is the second leading cause of death in Hungary as well as in the developed countries. The high cancer prevalence of the gastrointestinal tract is the result of the rapid turnover of epithelial cells and exposure to dietary toxins. Adult stem cells are in the lime-light of the medicine. The adult stem cells and tumor cells resemble to each other on the basis of their properties, like self-renewal and proliferation. Cancer is believed to be a disease of stem cells. Recent years have seen major advances in our understanding of location (niche), life cycle, regulation (Wnt/beta-catenin signaling pathway) and markers (mathusashi-1, beta-catenin) of gastrointestinal stem cells. The exact role of adult stem cells in intestinal carcinogenesis is open for debate. New works suggest the role for inflammation-induced engraftment of circulating marrow-derived stem cells in colorectal carcinogenesis. The causes of malignant transformation of local or engrafting bone marrow-derived stem cells are mutations (APC, MMR genes) or methylation (CDKN2A, p16/INK4a, MGMT, MLH1). The spread of dysplastic cells (bottom-up, top-down hypothesis) is also ambiguous.