Evidence that β1‐6 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 ‐GIcNAcβ1‐6Manαl‐6Manßi‐branched complex‐type Asn‐linked oligosaccharides in tumor‐cell glycoproteins. Here we demonstrate that cell‐surface expression of β1‐6 branched oligosaccharides in metastatic tumor cells is specifically associated with increased invasion of human amnion basement membranes in vitro. Compared to non‐metastatic SPI murine mammary carcinoma cells, 2 metastatic sublines expressed higher levels of β1‐6 branched oligosaccharides and were found to be invasive but poorly adhesive on the amnion basement membrane. Swainsonine, a non‐toxic inhibitor of β1‐linked oligosaccharide processing which blocks the pathway prior to initiation of the β1‐6 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, β‐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 β1‐6 branched complex‐type oligosaccharides at the tumor cell surface, such oligosaccharides being associated with reduced tumor‐cell adhesion to extracellular matrix.