[Differentiation of human colon cancer cells: a new approach to colon cancer]

Our purpose is to demonstrate that some human colon cancer cells are able to express the same differentiation features as normal intestinal epithelial cells and to report experimental data which suggest that these particular cells are spontaneously resistant and adaptable to anticancer drugs. The concept of normal differentiation of colon cancer cells is supported by observations made with two cultured cell lines, Caco-2 and HT-29. The cell line Caco-2 expresses spontaneously and homogeneously an enterocytic differentiation. The cell line HT-29 is heterogeneous as it contains a small proportion (< 5%) of differentiated cells of either enterocytic or mucus-secreting type. Homogeneous populations of differentiated HT-29 cells of either type have been isolated by pressure selection. In order to investigate whether the pressure associated with anti-cancer drugs would result in the selection of differentiated populations, HT-29 cells were cultured in the presence of increasing concentrations of methotrexate and 5-fluorouracil. The resulting resistant populations were found to be totally differentiated. This supports the view that the small proportion of parental cells which are able to differentiate are also able to spontaneously resist to drug pressure. These results imply that the concept of cellular differentiation should be considered by pathologists. They also imply that basic research should be developed in order to unravel which mechanisms of drug resistance are specifically associated with the ability of the cells to differentiate.