title: Immunization of A4galt-deficient mice with glycosphingolipids from renal cell cancers resulted in the generation of anti-sulfoglycolipid monoclonal antibodies.
abstract: In this study, we immunized Gb3/CD77 synthase gene (A4galt) knockout (KO) mice with glycosphingolipids (GSLs) extracted from 3 renal cell cancer (RCC) cell lines to raise monoclonal antibodies (mAbs) reactive with globo-series GSLs specifically expressed in RCCs. Although a number of mAbs reactive with globo-series GSLs were generated, they reacted with both RCC cell lines and normal kidney cells. When we analyzed recognized antigens by mAbs that were specifically reactive with RCC, but not with normal kidney cells at least on the cell surface, many of them turned out to be reactive with sulfoglycolipids. Eight out of 11 RCC-specific mAbs were reactive with SM2 alone, and the other 3 mAbs were more broadly reactive with sulfated glycolipids, i.e. SM3 and SM4 as well as SM2. In the immunohistochemistry, these anti-sulfoglycolipids mAbs showed RCC-specific reaction, with no or minimal reaction with adjacent normal tissues. Thus, immunization of A4galt KO mice with RCC-derived GSLs resulted in the generation of anti sulfated GSL mAbs, and these mAbs may be applicable for the therapeutics for RCC patients.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ando
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Tokuda
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: IMS, RIKEN Center for Integrative Medical Sciences, 1-7-22, Suehiro, Tsurumi-ku, Yokohama, 230-0045, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Xiaoen
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.|Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Research Center of Biomedical Analysis and Radioisotope, Teikyo University School of Medicine, 2-11-1, Kuga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Niimura
authors.affiliation: Institute of Glycoscience, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan.
authors.forename: Momokazu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-0065, Japan. koichi@med.nagoya-u.ac.jp.|Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan. koichi@med.nagoya-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D005700:Galactosyltransferases / Q000172:deficiency*; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D006801:Humans; D007114:Immunization; D007680:Kidney Neoplasms / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D006017:Glycolipids; C011117:sulfoglycolipids; D005700:Galactosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase
keywords: A4galt; Kidney; Monoclonal antibody; Renal cell cancer; Sulfoglycolipid