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Remodeling of glycoconjugates on CD44 enhances cell adhesion to hyaluronate, tumor growth and metastasis in B16 melanoma cells expressing β1,4‐N‐acetylglucosaminyltransferase III
Author(s) -
Sheng Yin,
Yoshimura Masafumi,
Inoue Shinya,
Oritani Kenji,
Nishiura Tetsuo,
Yoshida Hitoshi,
Ogawa Megumu,
Okajima Yu,
Matsuzawa Yuji,
Taniguchi Naoyuki
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971210)73:6<850::aid-ijc15>3.0.co;2-8
Subject(s) - cd44 , transfection , cell adhesion , glycoconjugate , adhesion , microbiology and biotechnology , biology , cell adhesion molecule , spleen , cancer research , chemistry , immunology , cell , biochemistry , gene , organic chemistry
β1–4 N‐acetylglucosaminyltransferase III (GnT‐III) synthesizes bisecting N‐acetylglucosamine structures on asparagine‐linked oligosaccharides. Using B16‐hm mouse melanoma cells stably expressing GnT‐III activity as positive transfectants, the effect of bisecting N‐acetylglucosamine on the function of CD44 was analyzed in association with adhesion to hyaluronate and tumor spread in mice. Transfection of GnT‐III caused increased affinity of immunoprecipitated CD44 to erythro‐agglutinating phytohemagglutinin, that preferentially recognizes bisecting N‐acetylglucosamine, without affecting the surface CD44 amount, indicating an increase in bisecting N‐acetylglucosamine residues on CD44 in positive transfectants. CD44‐mediated adhesion to immobilized hyaluronate and the binding of fluorescence‐labeled hyaluronate to the cell surface were increased in positive transfectants. The enhanced adhesion in positive transfectants was suppressed by the treatment with β‐N‐acetylhexosaminidase, indicating that N‐acetylglucosamine residues were responsible for the enhanced adhesion. Positive transfectants showed promoted CD44‐mediated tumor growth and metastatic development in the spleen after subcutaneous inoculation into mice. These results indicate that glycosylation of CD44 due to GnT‐III causes enhanced adhesion to hyaluronate, local tumor growth and metastatic growth in spleen, suggesting that the CD44‐mediated adhesion and tumor spread can be modified through introduction of a glycosyltransferase gene. Int. J. Cancer 73:850–858, 1997. © 1997 Wiley‐Liss, Inc.