Role of oligomannosidic N-glycans in the proliferation, adhesion and signalling of C6 glioblastoma cells.
The potential role of glycoprotein N-glycans in the proliferation and adhesion of C6 glioblastoma cells was investigated using a set of N-glycosylation inhibitors (tunicamycin, deoxynojirimycin, castanospermine, deoxymannojirimycin, swainsonine), and traffic (monensin). It was observed that both the proliferative and adhesive properties of C6 cells were dependent upon the expression at the cell surface of glycoproteins with oligomannosidic and hybrid type N-glycans, whereas the absence of N-glycans (tunicamycin) or the presence of glucosyl-oligomannosides (deoxynojirimycin and castanospermine) and the absence of glycoproteins at the cell surface (monensin) reduced both the proliferative and adhesive properties of C6 cells. Studies of the classical elements of signalling pathways indicated that the different inhibitors have a low impact on tyrosine phosphorylations and oncogene product expression (except the ras oncogene product), except on phosphorylations on other residues. An endogenous soluble lectin (CSL; J. Neurochem. 49 (1987) 1250), specific for oligomannosidic and hybrid type N-glycans, was present and externalised by the cells through a pinching-off of large intracellular vesicles, a mechanism that was not blocked by monensine; in contrast with the externalisation of its glycoprotein ligands. The inhibitory effect of anti-CSL Fab fragments on adhesion indicates that the polyvalent CSL acts as a bridging molecule for a family of surface glycoproteins expressed at the surface of C6 cells. The inhibitory effect of the same Fab fragments on the proliferation indicates that CSL is a mitogen for these cells, possibly involved in clustering its surface glycoprotein ligands. A mechanism for the loss of contact inhibition is discussed based on the over-expression of CSL ligands in C6 glioblastoma cells relative to normal cells.
Schraen-Maschke
S
S
Neuroendocrinologie et Physiologie Neuronale, INSERM U422, 1, Place de Verdun, 59045 Lille cedex, France.
Zanetta
J-P
JP
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D003260:Contact Inhibition; D005909:Glioblastoma; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007212:Indolizines / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008985:Monensin / Q000494:pharmacology; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D054836:Indolizidines
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007212:Indolizines; D037102:Lectins; D008024:Ligands; D008985:Monensin; D009844:Oligosaccharides; D011134:Polysaccharides; D014415:Tunicamycin; C059525:cerebellar soluble lectin; C028569:oligomannoside; C037806:castanospermine; D054836:Indolizidines