Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes.
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.
Yagel
S
S
Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Feinmesser
R
R
Waghorne
C
C
Lala
P K
PK
Breitman
M L
ML
Dennis
J W
JW
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
D000470:Alkaloids; D009844:Oligosaccharides; D010618:Phenanthrolines; D008666:Metalloendopeptidases; D017026:Swainsonine; C025205:1,10-phenanthroline