SUSCEPTIBILITY OF COLORECTAL-CARCINOMA CELLS TO NATURAL-KILLER-MEDIATED LYSIS - RELATIONSHIP TO CEA EXPRESSION AND DEGREE OF DIFFERENTIATION

This study addresses the relevance of cole rectal-carcinoma-cell (CRC) CEA expression and degree of differentiation in natural-killer(NK)-me diated lysis susceptibility. A Cr-51-release cytotoxicity assay perfor med with 5 human CRC lines demonstrated that CRC CEA expression was re lated to resistance to NK lysis. Moreover, the addition of anti-CEA Fa b fragments to the assay led to a significant increase of lysability o f high-CEA-producing and NK-resistant cells (LS 174-T), whereas purifi ed CEA drastically reduced lysis of low-CEA-producing and NK-susceptib le cells (LISP-I) in a dose-dependent manner. These results strongly s uggest that CEA plays a causal role in CRC resistance to NK lysis. Nev ertheless, our data did not demonstrate CEA binding to effector cell s urface, suggesting that CEA expression can protect CRC, possibly by pr eventing NK-tumor-cell adhesion to occur. Our results also show that C RC susceptibility to NK lysis was related to a less differentiated phe notype. HCT-8, which are poorly differentiated and low-CEA-producing c ells, were cultured in vitro in the presence of the differentiation ag ent sodium butyrate. Treated cells became less susceptible to NK lysis as they progressed towards a more differentiated phenotype. However, CEA production was not altered upon differentiation. Our study thus de monstrates that both features, CEA expression and degree of cellular d ifferentiation, may individually influence CRC susceptibility to NK ly sis. (C) 1995 Wiley-Liss, Inc.