REDUCTION OF LAK-SENSITIVITY AND CHANGES IN ANTIGEN EXPRESSION ON HEPATOMA-CELLS BY SODIUM-BUTYRATE

We demonstrated that sodium butyrate (SE) induced differentiation of f unctions in human hepatocellular carcinoma (HCC) cell lines. To invest igate relationship between the sensitivity for cellular cytotoxicity a nd the cellular differentiation of HCC cells, the effect of SE on lymp hokine-activated killer (LAK) sensitivity and antigen expression of a human HCC cells were studied. SE induced LAK-resistance of human HCC c ell lines, HCC-T and HCC-M, time-dependently. A flowcytometric analysi s of cell surface antigens revealed that SE markedly reduced the expre ssion of laminin and fibronectin and increased the expression of liver -specific antigen defined by a mouse monoclonal antibody time-dependen tly, but did not modify that of major histocompatibility complex antig ens, intercellular adhesion molecule (ICAM)-1, or CEA. Leukocyte funct ion-associated antigen (LFA)-3 expression on HCC-T was reduced slightl y by SE treatment. LAK sensitivity was inhibited by antilaminin, but n ot with anti-beta 2-microglobulin, anti-HLA DR, anti-ICAM-1, anti-fibr onectin, or anti-CEA. Anti-LFA-3 reduced LAK sensitivity of HCC-T, but not HCC-M, although the reduction was less than that obtained by anti -laminin treatment. These results provided evidence that SE induced LA K-resistance of human HCC cells according to cellular differentiation and extracellular matrix functionality played an important role in thi s LAK-mediated cell killing. Moreover, the structure expressed on HCC cells, which contributed to LAK cytolysis, was different for each HCC cell.