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

Abstract

The expressions of Lewis (Le) antigens, α-1,3/1,4 fucosyltransferases (α-1,3/1,4 FuTs), and metastatic potential after the treatment of 2 differentiation inducers, all- trans retinoic acid (ATRA), 8-bromo-cyclic 3′,5′adenosine monophosphate (8-Br-cAMP); and 2 proliferation inducers, epidermal growth factor (EGF) and phobol-12-myristate-13-acetate (PMA), on 7721 human hepatocarcinoma cell line were studied. Cell adhesion to human umbilical vein endothelial cells (HUVEC), cell migration through transwell and invasion through matrigel were selected as the indexes of metastatic potential-related phenotypes. Using fluorescence-labelled antibodies and flow-cytometric analysis, it was found that 7721 cells mainly expressed sialyl Lewis X (SLex) and a less amount of sialyl dimeric Lewis X (SDLex) antigens on the cell surface. Their expressions were down-regulated by ATRA, and up-regulated by EGF. SLexantigen was also decreased and increased by the treatment of 8-Br-cAMP and PMA respectively. With Northern blot to detect the mRNAs of α-1,3/1,4 FuTs, the main enzymatic basis for the change in SLexexpression was found to be the alteration of the expression of α-1,3 FuT-VII. It was evidenced by the observations that α-1,3 FuT-VII was the main α-1,3/1,4 FuT in 7721 cells, while α-1,3/1,4 FuT-III and α-1,3 FuT-VI were expressed rather low. The changes in the expressions of SLexantigen and α-1,3 FuT-VII resulted in the altered cell adhesion to tumour necrosis factor-α stimulated HUVEC, since only the monoclonal antibody of the SLex, but not other monoclonal antibodies blocked the 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 EGF or PMA. The above findings indicate that the metastatic potential of 7721 cells is suppressed by differentiation-inducers and promoted by proliferation-inducers. © 2001 Cancer Research Campaign http://www.bjcancer.com