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Increased Expression of Highly Branched N-Glycans at Cell Surface Is Correlated with the Malignant Phenotypes of Mouse Tumor Cells¹

Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108 [M. A., K. F., T. E., A. K.]; Biosignaling Department, National Institute of Bioscience and Human-Technology, Tsukuba, Ibaraki 305 [M.A.]; and Department of Microbiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160, Japan [K. S.]

Three NIH3T3 transformants, MTAg, MTPy, and MT1, which grow similarly in soft agar media, showed remarkable differences in athymic mice: MTAg grew more rapidly than MTPy, whereas MT1 and NIH3T3 did not, and only MTAg metastasized in lung. Structural analysis of N-glycans from plasma membrane glycoproteins revealed that each sample contains similar amounts of N-glycans, but the relative amounts of 2,6-branched tri- and tetra-antennary oligosaccharides prominently increase and the relative amounts of biantennary oligosaccharides prominently decrease in the order of NIH3T3, MT1, MTPy, and MTAg, whereas those of others remained constant. Western blot analysis revealed that binding of Datura stramonium agglutinin, which interacts with 2,6-branched tri- and tetra-antennary oligosaccharides, is significantly increased in several bands from MTAg compared with NIH3T3, two of which are tentatively identified as lysosome-associated membrane protein-1 and fibronectin (FN)-receptor. It was also shown that the spreading of MTAg on FN-coated plates is dramatically inhibited with the anti-FN-receptor antiserum when compared with NIH3T3. These results indicate that the increased expression of highly branched N-glycans at cell surface is correlated with the rapidness of tumor formation and altered adhesive properties of tumor cells in vivo.

¹ This work was supported by grants-in-aid for scientific research from the Ministry of Education, Sciences, Sports, and Culture of Japan, and by a research grant from the Japanese Society of the Promotion of Science for Japanese Junior Scientists (to M. A.).

² To whom requests for reprints should be addressed, at Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173, Japan. Phone: 81-3-3964-3241, ext. 3071; Fax: 81-3-3579-4776; E-mail: furukawa@tmig.or.jp.

³ Present address: Department of Biosignal Research (K. F.), Department of Glycobiology (T. E.), and Director's Office (A. K.), Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173, Japan.

Received 10/25/96. Accepted 1/20/97.

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