Open AccessModulation of carcinoembryonic antigen release by glucosylceramide
Author(s) -
Babia Teresa,
Veldman Robert Jan,
Hoekstra Dick,
Kok Jan Willem
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2580233.x
Subject(s) - carcinoembryonic antigen , microbiology and biotechnology , ceramide , chemistry , intracellular , glycolipid , cellular differentiation , villin , cell , biochemistry , biology , actin , cancer , apoptosis , genetics , gene
Previous work suggested that glucosylceramide (GlcCer) plays a role in the regulation of cell differentiation of HT29 human colon tumor cells [1]. 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 were treated with D , L ‐ threo ‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol (PDMP), 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 results demonstrate that PDMP causes an increase in the release of CEA, while exogenous C 6 ‐GlcCer suppresses its release. Furthermore, the enhanced release of CEA in the presence of PDMP, could be completely reversed upon exogenous addition of C 6 ‐GlcCer. Control experiments reveal that a potential interference of the well‐known modulator of cell physiology, 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 cytoskeletal protein villin. These results, together with the observations on modulation of the differentiation marker CEA by GlcCer, provide support for the conclusion that GlcCer interferes with the differentiation of HT29 cells.