Colon Cancer Cell Differentiation as Related to Methotrexate and 5-Fluorouracil Resistance

Abstract

Colon cancer is a major health problem because of its high frequency and the poor outcome of invasive forms, due to their overall resistance to chemotherapy. Although it has been assumed that drug resistance could be associated with some particular cell populations, these have not been characterized yet. It is only in recent years that progress in the field of intestinal cell biology, based on the development of cultured cell lines and availability of immunological and molecular probes, has allowed to characterize cells at the Single cell level and to study their Organization and functions. This has led to the concept of colon cancer cell differentiation. Cellular differentiation, which should not be confused with differentiation of colon cancers as defined by pathologists, is the ability of colon cancer cells to express, in vitro and in vivo, the same morphological and functional characteristics as normal epithelial intestinal cells, i.e. enterocytes or goblet cells. Whether these cells, which behave like normal cells as to their differentiation characteristics and functions, possess particular adaptation properties which allow them to escape the cytotoxic effect of a number of stress conditions, including treatment with anti-cancer drugs, is based on recent experimental data obtained with cultured human colon cancer cell lines. The purpose of this article is to (1) summarize our knowledge on colon cancer cell differentiation and show how experience in the field of cell biology can be transferred to clinical situations and (2) focus on experimental data which suggest that drug resistance is associated with cellular differentiation.