Regulation of differentiation- and proliferation-inducers on Lewis antigens, alpha-fucosyltransferase and metastatic potential in hepatocarcinoma cells

The expressions of Lewis (Le) antigens, alpha -1,3/1,4 fucosyltransferases (alpha -1,3/1,4 FuTs), and metastatic potential after the treatment of 2 di fferentiation inducers, all-trans retinoic acid (ATRA), 8-bromo-cyclic 3',5 'adenosine monophosphate (8-Br-cAMP); and 2 proliferation inducers, epiderm al growth factor (EGF) and phobol-12-myristate-13-acetate (PMA), on 7721 hu man hepatocarcinoma cell line were studied, Cell adhesion to human umbilica l vein endothelial cells (HUVEC), cell migration through transwell and inva sion through matrigel were selected as the indexes of metastatic potential- related phenotypes. Using fluorescence-labeled antibodies and flow-cytometr ic analysis, it was found that 7721 cells mainly expressed sialyl Lewis X ( SLe(x)) and a less amount of sialyl dimeric Lewis X (SDLe(x)) antigens on t he cell surface. Their expressions were down-regulated by ATRA, and up-regu lated by EGF. SLe(x) antigen was also decreased and increased by the treatm ent of 8-Br-cAMP and PMA respectively With Northern blot to detect the mRNA s of alpha -1,3/1,4 FuTs, the main enzymatic basis for the change in SLe(x) expression was found to be the alteration of the expression of alpha -1,3 FuT-VII. it was evidenced by the observations that alpha -1,3 FuT-VII was t he main alpha -1,3/1,4 FuT in 7721 cells,while alpha -1,3/1,4 FuT-III and a lpha -1,3 FuT-VI were expressed rather low. The changes in the expressions of SLe(x) antigen and alpha -1,3 FuT-VII resulted in the altered cell adhes ion to tumour necrosis factor-alpha stimulated HUVEC, since only the monocl onal antibody of the SLe(x), but not other monoclonal antibodies blocked th e adhesion of 7721 cells to HUVEC. The migration and invasion of 7721 cells were also reduced by the treatment of ATRA or 8-Br-cAMP, and elevated by E GF or PMA. The above findings indicate that the metastatic potential of 772 1 cells is suppressed by differentiation-inducers and promoted by prolifera tion-inducers. (C) 2001 Cancer Research Campaign.