title: An antibody to de-N-acetyl sialic acid containing-polysialic acid identifies an intracellular antigen and induces apoptosis in human cancer cell lines.
abstract: Polysialic acid (PSA), an α2,8-linked homopolymer of N-acetylneuraminic acid (Neu5Ac), is developmentally regulated and its expression is thought to be restricted to a few tissues in adults. Recently, we showed that two human pathogens expressed a derivative of PSA containing de-N-acetyl sialic acid residues (NeuPSA). Here we show that an epitope identified by the anti-NeuPSA monoclonal antibody, SEAM 3 (SEAM 3-reactive antigen or S3RA), is expressed in human melanomas, and also intracellularly in a human melanoma cell line (SK-MEL-28), a human T cell leukemia cell line (Jurkat), and two neuroblastoma cell lines (CHP-134 and SH-SY5Y). SEAM 3 binding induced apoptosis in the four cell lines tested. The unusual intracellular distribution of S3RA was similar to that described for the PSA polysialyltransferases, STX and PST, which are also expressed in the four cell lines used here. Interestingly, suppression of PST mRNA expression by transfection of SK-MEL-28 cells with PST-specific short interfering RNA (siRNA) resulted in decreased SEAM 3 binding. The results suggest further studies of the utility of antibodies such as SEAM 3 as therapeutic agents for certain malignancies.
authors.affiliation: Centers for Cancer, Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Steirer
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Moe
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D015458:Leukemia, T-Cell / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology; D012794:Sialic Acids / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D012794:Sialic Acids; C021319:polysialic acid
references.citation: BMC Cancer. 2009 Feb 17;9:57
references.pmid: 19222860
references.citation: J Immunol. 1998 May 15;160(10):5028-36
references.pmid: 9590252
references.citation: Cancer Res. 1990 Feb 15;50(4):1102-6
references.pmid: 2153450
references.citation: Glycobiology. 2006 May;16(5):375-89
references.pmid: 16481330
references.citation: Differentiation. 1994 Aug;57(2):119-31
references.pmid: 8070624
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10250-5
references.pmid: 20479255
references.citation: Mol Immunol. 2006 Mar;43(9):1424-31
references.pmid: 16140379
references.citation: J Biol Chem. 2001 Sep 7;276(36):33657-64
references.pmid: 11418585
references.citation: Glycobiology. 2007 Apr;17(4):367-73
references.pmid: 17242043
references.citation: J Biol Chem. 1994 Jan 21;269(3):1959-65
references.pmid: 7507488
references.citation: J Biol Chem. 2003 Dec 5;278(49):49031-43
references.pmid: 14506234
references.citation: Am J Pathol. 1988 Nov;133(2):227-40
references.pmid: 2461089
references.citation: J Biol Chem. 1990 Aug 5;265(22):13091-103
references.pmid: 2198284
references.citation: BMC Cancer. 2010 Mar 10;10:91
references.pmid: 20219118
references.citation: Acta Neurochir (Wien). 2009 Jun;151(6):601-3; discussion 603-4
references.pmid: 19387537
references.citation: Biochem Biophys Res Commun. 1983 Apr 29;112(2):482-7
references.pmid: 6847662
references.citation: Acta Dermatovenerol Croat. 2009;17(3):209-16
references.pmid: 19818222
references.citation: Biochim Biophys Acta. 1985 Dec 4;837(3):349-53
references.pmid: 3840699
references.citation: J Neurobiol. 2001 Jan;46(1):11-28
references.pmid: 11108612
references.citation: J Biol Chem. 1992 May 15;267(14):9965-71
references.pmid: 1315775
references.citation: J Immunol. 2009 May 15;182(10):6610-7
references.pmid: 19414816
references.citation: J Biol Chem. 2002 May 17;277(20):17502-10
references.pmid: 11884388
references.citation: Sci Signal. 2009 Nov 24;2(98):ra76
references.pmid: 19934434
references.citation: Cancer Res. 2000 Jun 1;60(11):3072-80
references.pmid: 10850459
references.citation: J Biol Chem. 2003 Apr 18;278(16):13875-80
references.pmid: 12576469
references.citation: J Biol Chem. 1998 Dec 18;273(51):34586-93
references.pmid: 9852130
references.citation: Pediatr Res. 1998 Jan;43(1):145-7
references.pmid: 9432126
references.citation: J Immunol. 1982 Nov;129(5):2172-8
references.pmid: 6811660
references.citation: Cancer Res. 1999 Mar 15;59(6):1337-46
references.pmid: 10096568
references.citation: Exp Cell Res. 1994 Apr;211(2):314-21
references.pmid: 8143779
references.citation: Biochem Biophys Res Commun. 1987 Aug 31;147(1):127-34
references.pmid: 3498483
references.citation: Vaccine. 2010 Aug 23;28(37):5967-72
references.pmid: 20637761
references.citation: J Neurochem. 1999 Feb;72(2):514-21
references.pmid: 9930722
references.citation: Curr Opin Struct Biol. 2009 Oct;19(5):507-14
references.pmid: 19699080
references.citation: Infect Immun. 2005 Apr;73(4):2123-8
references.pmid: 15784554
references.citation: J Biol Chem. 1995 Feb 17;270(7):2921-30
references.pmid: 7852370
references.citation: J Biol Chem. 1988 May 5;263(13):6296-301
references.pmid: 2834372
references.citation: IEEE Trans Med Imaging. 2002 Apr;21(4):296-304
references.pmid: 12022618
references.citation: J Microsc. 2006 Dec;224(Pt 3):213-32
references.pmid: 17210054
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11995-2000
references.pmid: 19587240
references.citation: Trends Biochem Sci. 1994 Mar;19(3):124-8
references.pmid: 8203019
references.citation: Nat Rev Neurosci. 2008 Jan;9(1):26-35
references.pmid: 18059411
references.citation: J Eukaryot Microbiol. 2010 Sep-Oct;57(5):405-14
references.pmid: 20707828
references.citation: J Biol Chem. 2007 Oct 19;282(42):30346-56
references.pmid: 17699524