title: Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes.
abstract: Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a l-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, D-galactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent d-mannose and d-xylose, respectively), underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycans.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Shih-Fen
authors.initials: SF
authors.lastname: Liao
authors.forename: Chi-Hui
authors.initials: CH
authors.lastname: Liang
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Ho
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.forename: Tsung-I
authors.initials: TI
authors.lastname: Tsai
authors.forename: Yves S-Y
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Tsai
authors.forename: Shiou-Ting
authors.initials: ST
authors.lastname: Li
authors.forename: Yang-Yu
authors.initials: YY
authors.lastname: Cheng
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Tsao
authors.forename: Tung-Yi
authors.initials: TY
authors.lastname: Lin
authors.forename: Zong-Yan
authors.initials: ZY
authors.lastname: Lin
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Yang
authors.forename: Chien-Tai
authors.initials: CT
authors.lastname: Ren
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Hsien-Yeh
authors.initials: HY
authors.lastname: Hsu
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D018932:Chemokine CCL2 / Q000378:metabolism; D005643:Fucose / Q000276:immunology*; D062610:Fungal Polysaccharides / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D007075:Immunoglobulin M / Q000097:blood / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D020940:Reishi / Q000737:chemistry*
chemical_list: D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018932:Chemokine CCL2; D062610:Fungal Polysaccharides; C472765:Globo-H; D007075:Immunoglobulin M; D005643:Fucose
keywords: anti-Globo H antibody; antitumor activity; mushroom polysaccharide
references.citation: Front Pharmacol. 2012 Jul 13;3:135
references.pmid: 22811667
references.citation: J Biochem. 1981 Apr;89(4):1029-37
references.pmid: 6894749
references.citation: Appl Microbiol Biotechnol. 2002 Nov;60(3):258-74
references.pmid: 12436306
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2517-22
references.pmid: 23355685
references.citation: J Cell Physiol. 2007 Aug;212(2):537-50
references.pmid: 17474083
references.citation: Oncol Rep. 2003 Mar-Apr;10(2):375-9
references.pmid: 12579275
references.citation: Curr Drug Targets Infect Disord. 2001 Nov;1(3):325-34
references.pmid: 12455405
references.citation: Immunity. 2001 May;14(5):617-29
references.pmid: 11371363
references.citation: J Immunol. 2009 Nov 15;183(10):6359-68
references.pmid: 19841173
references.citation: Adv Exp Med Biol. 2001;491:369-402
references.pmid: 14533809
references.citation: Histochem J. 1995 Mar;27(3):247-52
references.pmid: 7797428
references.citation: Bioorg Med Chem. 2002 Apr;10(4):1057-62
references.pmid: 11836115
references.citation: Acta Chem Scand. 1971;25(10):3645-50
references.pmid: 5004880
references.citation: Crit Rev Immunol. 1999;19(1):65-96
references.pmid: 9987601
references.citation: Cancer Res. 1983 Mar;43(3):1295-300
references.pmid: 6337705
references.citation: Nat Rev Drug Discov. 2005 Jun;4(6):477-88
references.pmid: 15931257
references.citation: J Immunol Methods. 1994 Sep 14;174(1-2):155-65
references.pmid: 8083517
references.citation: Bioorg Med Chem. 2004 Nov 1;12(21):5595-601
references.pmid: 15465337
references.citation: Science. 1994 Sep 2;265(5177):1385-7
references.pmid: 8073278
references.citation: Glycoconj J. 1996 Aug;13(4):585-90
references.pmid: 8872115
references.citation: Expert Rev Vaccines. 2009 Oct;8(10):1399-413
references.pmid: 19803761
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11661-6
references.pmid: 18689688
references.citation: Carbohydr Res. 2008 Mar 17;343(4):746-52
references.pmid: 18179790
references.citation: J Med Food. 2005 Summer;8(2):159-68
references.pmid: 16117607
references.citation: Nat Rev Drug Discov. 2010 Apr;9(4):308-24
references.pmid: 20357803
references.citation: J Biol Chem. 1984 Dec 10;259(23):14773-7
references.pmid: 6501317
references.citation: FEMS Microbiol Lett. 2004 Jan 15;230(1):47-52
references.pmid: 14734165
references.citation: J Natl Cancer Inst. 2008 Oct 15;100(20):1464-76
references.pmid: 18840818
references.citation: Jpn J Cancer Res. 1993 Jun;84(6):664-72
references.pmid: 8340255
references.citation: J Biol Chem. 1986 Jan 25;261(3):1388-92
references.pmid: 3944092
references.citation: Immunol Cell Biol. 2005 Aug;83(4):418-28
references.pmid: 16033538
references.citation: Curr Opin Hematol. 2003 Jan;10(1):16-24
references.pmid: 12483107
references.citation: Glycoconj J. 1996 Apr;13(2):263-71
references.pmid: 8737251
references.citation: Proc Natl Acad Sci U S A. 1985 Feb;82(4):1199-203
references.pmid: 2579390
references.citation: Immunol Invest. 2005;34(2):171-98
references.pmid: 15921158
references.citation: Planta Med. 2008 Nov;74(14):1730-4
references.pmid: 18683124
references.citation: Vaccine. 2010 Jul 12;28(31):4945-54
references.pmid: 20653103
references.citation: Bioorg Med Chem. 2010 Dec 15;18(24):8583-91
references.pmid: 21055951
references.citation: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5710-5
references.pmid: 10318949
references.citation: J Biol Chem. 2006 Aug 25;281(34):24111-23
references.pmid: 16798741
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3270-5
references.pmid: 11248068
references.citation: Acta Pharmacol Sin. 2004 Jun;25(6):833-8
references.pmid: 15169641
references.citation: Chem Pharm Bull (Tokyo). 1981 Dec;29(12):3611-6
references.pmid: 7340947
references.citation: Carbohydr Res. 2002 Apr 17;337(8):719-30
references.pmid: 11950468
references.citation: J Biol Chem. 2009 Dec 11;284(50):34479-89
references.pmid: 19837675
references.citation: Am J Respir Cell Mol Biol. 2011 Feb;44(2):230-7
references.pmid: 20395632
references.citation: Immunity. 2004 Sep;21(3):379-90
references.pmid: 15357949
references.citation: BMJ. 2000 Sep 16;321(7262):683-6
references.pmid: 10987776