Tunicamycin treatment reduces intracellular glutathione levels: Effect on the metastatic potential of the rhabdomyosarcoma cell line S4MH

Highly metastatic cells are known to overexpress certain Asn-linked oligosa ccharides in the plasmatic membrane. Another phenotypic characteristic of m alignant cells consists in the expression of high levels of intracellular g lutathione (GSH). The aim of the present work was to demonstrate that the i nhibition of N-glycosylation induces changes in intracellular GSH levels, a nd in turn participates in the inhibition of the metastatic potential of tu mor cells by tunicamycin treatment. Firstly, we demonstrated that in compar ison to the poorly metastatic cell line F21, the highly metastatic cells SI MH express a higher number of Asn-linked beta1-6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins i nvolved in the regulation of the adhesion efficiency of tumor cells on endo thelial cells and extracellular matrix:. Our results showed that the decrea se in S4MH cell adhesion efficiency on endothelial cells and extracellular matrix after the inhibition of N-glycan processing by tunicamycin treatment was caused by: (1) inhibition of the expression of N-glycan structures rec ognized by endothelial endogenous lectins, including beta1-6 branched oligo saccharides and SA and/or chitobiose oligosaccharides, and (2) redistributi on of cell surface glycoproteins with beta1-6 branched oligosaccharides and /or SA and/or chitobiose oligosaccharides in their structures, caused by th e depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cell! ; necessary for anchoring to the substratum. Copyright (C) 2000 S. Karger A G, Basel.