title: Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes.
abstract: In previous studies we have shown that the ability of murine tumor cells to metastasize in situ is directly linked to expression of -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched complex-type Asn-linked oligosaccharides in tumor-cell glycoproteins. Here we demonstrate that cell-surface expression of beta 1-6 branched oligosaccharides in metastatic tumor cells is specifically associated with increased invasion of human amnion basement membranes in vitro. Compared to nonmetastatic SP1 murine mammary carcinoma cells, 2 metastatic sublines expressed higher levels of beta 1-6 branched oligosaccharides and were found to be invasive but poorly adhesive on the amnion basement membrane. Swainsonine, a non-toxic inhibitor of Asn-linked oligosaccharide processing which blocks the pathway prior to initiation of the beta 1-6 linked antenna, blocked metastatic tumor-cell invasion and increased adhesiveness. Swainsonine and the metalloprotease inhibitor O-phenanthroline inhibited invasion, apparently via independent mechanisms. O-phenanthroline did not affect tumor-cell adhesion to the amnion basement membrane and swainsonine did not block secretion of metalloproteases, beta-hexosaminadase or tissue plasminogen activator activity by the tumor cells. These results suggest that tumor-cell invasion of basement membranes requires both secretion of hydrolase activities and expression of beta 1-6 branched complex-type oligosaccharides at the tumor cell surface, such oligosaccharides being associated with reduced tumor-cell adhesion to extracellular matrix.
authors.affiliation: Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Yagel
authors.forename: R
authors.initials: R
authors.lastname: Feinmesser
authors.forename: C
authors.initials: C
authors.lastname: Waghorne
authors.forename: P K
authors.initials: PK
authors.lastname: Lala
authors.forename: M L
authors.initials: ML
authors.lastname: Breitman
authors.forename: J W
authors.initials: JW
authors.lastname: Dennis
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000650:Amnion / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009844:Oligosaccharides / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D017026:Swainsonine; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D009844:Oligosaccharides; D010618:Phenanthrolines; D008666:Metalloendopeptidases; D017026:Swainsonine; C025205:1,10-phenanthroline