MODULATION OF CARCINOEMBRYONIC ANTIGEN RELEASE BY GLUCOSYLCERAMIDE - IMPLICATIONS FOR HT29 CELL-DIFFERENTIATION

Previous work suggested that glucosylceramide (GlcCer) plays a role in the regulation of cell differentiation of HT29 human colon tumor cell s [I]. In the present study, we investigated the role of GlcCer in the cellular release of carcinoembryonic antigen (CEA), a marker for cell differentiation. This was done by modulating the intracellular level of the glycolipid, according to two different approaches. The cells we re treated with o-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PD MP), which resulted in a specific lowering of the cellular GlcCer pool . Alternatively, by exogenous addition of a short-chain analog of the lipid, hexanoyl(C-6)-GlcCer, the cellular pool was enhanced. The resul ts demonstrate that PDMP causes an increase in the release of CEA, whi le exogenous C-6-GlcCer suppresses its release. Furthermore, the enhan ced release of CEA in the presence of PDMP, could be completely revers ed upon exogenous addition of C-6-GlcCer. Control experiments reveal t hat a potential interference of the well-known modulator of cell physi ology, ceramide (Cer), can be excluded. Long-term depletion of GlcCer resulted in a change in a morphological feature of differentiation of the cells, i.e. an increase in apical membrane surface with microvilli brush borders, accompanied by an enhanced expression of the cytoskele tal protein villin. These results, together with the observations on m odulation of the differentiation marker CEA by GlcCer, provide support for the conclusion that GlcCer interferes with the differentiation of HT29 cells.