Tunicamycin Treatment Reduces Intracellular Glutathione Levels: Effect on the Metastatic Potential of the Rhabdomyosarcoma Cell Line S4MH

Abstract

Highly metastatic cells are known to overexpress certain Asn-linked oligosaccharides in the plasmatic membrane. Another phenotypic characteristic of malignant cells consists in the expression of high levels of intracellular glutathione (GSH). The aim of the present work was to demonstrate that the inhibition of N-glycosylation induces changes in intracellular GSH levels, and in turn participates in the inhibition of the metastatic potential of tumor cells by tunicamycin treatment. Firstly, we demonstrated that in comparison to the poorly metastatic cell line F21, the highly metastatic cells S4MH express a higher number of Asn-linked β1–6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins involved in the regulation of the adhesion efficiency of tumor cells on endothelial cells and extracellular matrix. Our results showed that the decrease 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 recognized by endothelial endogenous lectins, including β1–6 branched oligosaccharides and SA and/or chitobiose oligosaccharides, and (2) redistribution of cell surface glycoproteins with β1–6 branched oligosaccharides and/or SA and/or chitobiose oligosaccharides in their structures, caused by the depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cells necessary for anchoring to the substratum.

Modification of Glycosylation Mediates the Invasive Properties of Murine Hepatocarcinoma Cell Lines to Lymph Nodes

“…Inhibition of N-glycan processing disrupts normal cell adhesion and reduces the tumourigenic and metastatic capacity in vivo of rhabdomyosarcoma cell line S4MH [32]. Deglycosylation of Hca-F cells by tunicamycin influences on cells adhesion in vitro [33].…”

Potentiation of Lipid Peroxidation in B16F10 and B16F1 Melanoma Cells by Caffeine, a Methylxanthine Derivative: Relationship to Intracellular Glutathione

“…Some reports revealed the correlation of GSH content with the metastatic activity of melanoma cells [27][28][29]. In the present study, we also reported a higher value of intracellular GSH in high potential metastatic B16F10 melanoma cells (45.22 nmol/10 6 cells) in comparison to low potential metastatic B16F1 melanoma cells (29.11 nmol/ 10 6 cells).…”

N-Glycosylation Regulates ADAM8 Processing and Activation

“…Notably, N-glycosylation participates in the adherence of circulating tumor cells to the microvascular bed essential for extravasation and facilitates metastasis from the blood or lymph to other organs (26). Consistently, treatment of the highly aggressive sarcoma cell line S4MH with the N-glycosylation inhibitor tunicamycin resulted in loss of tumor cell adherence to endothelial cells and a significant reduction in the metastatic capacity (27). Murine ADAM8 was shown to be N-glycosylated (28).…”