Control of differentiation in human colorectal carcinoma cell lines: Epithelial—mesenchymal interactions

Mesenchymal elements have been investigated for their effects on the growth and differentiation of seven human colorectal carcinoma-derived cell lines. Epithelial cells were cultured as monolayers on plastic; they were also grown on fibroblast lawns and in collagen matrices, with and without fibroblasts. In each case, differentiation was assessed morphologically with monoclonal antibodies directed against components of normal goblet and columnar cells. The results were compared with those obtained when the cell lines were grown in vivo as xenografts in athymic mice. The xenografts allowed the greatest potential for differentiation, although two cell lines showed little or no response to mesenchyme either in vivo or in vitro. The presence of fibroblasts induced branched structures in all the remaining lines when these were cultured in collagen matrices. The collage matrix alone induced the formation of well-defined glandular structures in SW1222 cells, reminiscent of those seen in SW1222 xenografts and normal colonic crypts. Epithelial response to mesenchymal factors may require specific receptors, the expression of which dictates phenotype. Isolation and analysis of such receptors and factors could lead to clarification of the mechanisms underlying normal tissue morphogenesis and the growth and spread of neoplastic cells.