Suppression of lung metastasis of B16 mouse melanoma by N-acetylglucosaminyltransferase III gene transfection.

Abstract

The beta 1-6 structure of N-linked oligosaccharides, formed by beta-1,6-N-acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential. We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1 murine melanoma cells. The gene encoding beta-1,4-N-acetylglucosaminyltransferase (GnT-III) was introduced into the B16-hm cells, and three clones that stably expressed high GnT-III activity were obtained. In these transfectants, the affinity to leukoagglutinating phytohemagglutinin was reduced, whereas the binding to erythroagglutinating phytohemagglutinin was increased, indicating that the level of beta 1-6 structure was decreased due to competition for substrate between intrinsic GnT-V and ectopically expressed GnT-III. Lung metastasis after intravenous injection of the transfectants into syngeneic and nude mice was significantly suppressed, suggesting that the decrease in beta 1-6 structure suppressed metastasis via a mechanism independent of the murine system. These transfectants also displayed decreased invasiveness into Matrigel and inhibited cell attachment to collagen and laminin. Cell growth was not affected. Our results demonstrate a causative role for beta 1-6 branches in invasion and cell attachment in the extravasation stage of metastasis.

• Authors: M Yoshimura, A Nishikawa, Y Ihara, S Taniguchi, N Taniguchi
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 92 Issue 19 Pg. 8754-8 (Sep 12 1995) ISSN: 0027-8424 [Print] United States
• PMID: 7568011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lectins
• Oligosaccharides
• N-Acetylglucosaminyltransferases
• beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
• N-Acetyllactosamine Synthase

Topics

• Agglutination
• Animals
• Carbohydrate Sequence
• Cell Adhesion
• Cell Division
• Clone Cells
• Lectins (metabolism)
• Lung Neoplasms (secondary)
• Melanoma, Experimental (secondary)
• Mice
• Molecular Sequence Data
• N-Acetylglucosaminyltransferases (genetics, metabolism)
• N-Acetyllactosamine Synthase (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Oligosaccharides (biosynthesis, chemistry)
• Transfection