Epidermal growth factor receptor expression in primary cultured human colorectal carcinoma cells

In situ hybridization on human colon tissue demonstrates that epidermal gro wth factor receptor (EGFR) mRNA expression is strongly increased during tum our progression. To obtain test systems to evaluate the relevance of growth factor action during carcinogenesis, primary cultures from human colorecta l carcinomas were established. EGFR distribution was determined in 2 of the 27 primary cultures and was compared with that in well-defined subclones d erived from the Caco-2 cell line, which has the unique property to differen tiate spontaneously in vitro in a manner similar to normal enterocytes. The primary carcinoma-derived cells had up to three-fold higher total EGFR lev els than the Caco-2 subclones and a basal mitotic rate at least fourfold hi gher. The EGFR affinity constant is 0.26 nmol l(-1), which is similar to th at reported in Caco-2 cells. The proliferation rate of Caco-2 cells is main ly induced by EGF from the basolateral cell surface where the majority of r eceptors are located, whereas primary cultures are strongly stimulated from the apical side also. This corresponds to a three- to fivefold higher leve l of EGFR at the apical cell surface. This redistribution of EGFR to apical plasma membranes in advanced colon carcinoma cells suggests that autocrine growth factors in the colon lumen may play a significant role during tumou r progression.