Cancer intelligence acquired (CIA): Tumor glycosylation and sialylation codes dismantling antitumor defense

Cellular and Molecular Life Sciences

Volumn 72, Issue 7, 2015, Pages 1231-1248

  Boligan, Kayluz Frias ^a   Mesa, Circe ^b   Fernandez, Luis Enrique ^b   Von Gunten, Stephan ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b CENTER OF MOLECULAR IMMUNOLOGY   (Cuba)

Author keywords

Altered branching; Cancer glycosylation; Cancer immunoediting; Sialoglycans; Tumor immunosuppression; Xeno autosialylation

Indexed keywords

CANCER VACCINE; GALECTIN; GLYCAN; HEPARIN; IMMUNOGLOBULIN; LECTIN; LOW MOLECULAR WEIGHT HEPARIN; N ACETYLGLUCOSAMINYLTRANSFERASE; PLACEBO; RACOTUMOMAB; SELECTIN; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; N ACETYLNEURAMINIC ACID; POLYSACCHARIDE;

ACUTE MYELOBLASTIC LEUKEMIA; ADAPTIVE IMMUNITY; ANTIINFLAMMATORY ACTIVITY; BASAL CELL CARCINOMA; BLADDER TUMOR; BREAST CANCER; BURKITT LYMPHOMA; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CARBOHYDRATE SYNTHESIS; CHRONIC LYMPHATIC LEUKEMIA; COLORECTAL CANCER; CUTANEOUS T CELL LYMPHOMA; DRUG MEGADOSE; DRUG TARGETING; GLYCOSYLATION; HUMAN; IMMUNE RESPONSE; IMMUNOSURVEILLANCE; INNATE IMMUNITY; MALIGNANT TRANSFORMATION; MELANOMA; METASTASIS; METASTASIS INHIBITION; NATURAL KILLER CELL; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CARCINOMA; PROSTATE CANCER; PROTEIN CARBOHYDRATE INTERACTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIALYLATION; SQUAMOUS CELL CARCINOMA; TUMOR ESCAPE; TUMOR GROWTH; TUMOR IMMUNITY; BIOLOGICAL MODEL; GENETICS; METABOLISM; NEOPLASMS;

GLYCOSYLATION; HUMANS; LECTINS, C-TYPE; MODELS, BIOLOGICAL; N-ACETYLNEURAMINIC ACID; NEOPLASMS; POLYSACCHARIDES; SELECTINS; SIALIC ACID BINDING IMMUNOGLOBULIN-LIKE LECTINS;

EID: 84930909270     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-014-1799-5     Document Type: Review

References (175)

1. Hart GW, Copeland RJ (2010) Glycomics hits the big time. Cell 143(5):672-676. doi: 10.1016/j.cell.2010.11.008
2. Schachter H, Freeze HH (2009) Glycosylation diseases: quo vadis? Biochim Biophys Acta 1792(9):925-930. doi: 10.1016/j.bbadis.2008.11.002
3. Varki A (2006) Nothing in glycobiology makes sense, except in the light of evolution. Cell 126(5):841-845. doi: 10.1016/j.cell.2006.08.022
4. Gagneux P, Varki A (1999) Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9(8):747-755
5. North SJ, von Gunten S, Antonopoulos A, Trollope A, MacGlashan DW Jr, Jang-Lee J, Dell A, Metcalfe DD, Kirshenbaum AS, Bochner BS, Haslam SM (2012) Glycomic analysis of human mast cells, eosinophils and basophils. Glycobiology 22(1):12-22. doi: 10.1093/glycob/cwr089
6. Stanley P, Cummings RD (2009) Structures common to different glycans. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York
7. Ohtsubo K, Marth JD (2006) Glycosylation in cellular mechanisms of health and disease. Cell 126(5):855-867. doi: 10.1016/j.cell.2006.08.019
8. Häuselmann I, Borsig L (2014) Altered tumor-cell glycosylation promotes metastasis. Front Oncol 4:28. doi: 10.3389/fonc.2014.00028
9. Fuster MM, Esko JD (2005) The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5(7):526-542. doi: 10.1038/nrc1649
10. Gabius HJ (2000) Biological information transfer beyond the genetic code: the sugar code. Naturwissenschaften 87(3):108-121
11. Stowell SR, Arthur CM, McBride R, Berger O, Razi N, Heimburg-Molinaro J, Rodrigues LC, Gourdine JP, Noll AJ, von Gunten S, Smith DF, Knirel YA, Paulson JC, Cummings RD (2014) Microbial glycan microarrays define key features of host-microbial interactions. Nat Chem Biol 10(6):470-476. doi: 10.1038/nchembio.1525
12. von Gunten S, Smith DF, Cummings RD, Riedel S, Miescher S, Schaub A, Hamilton RG, Bochner BS (2009) Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclass. J Allergy Clin Immunol 123(6):1268-1276. doi: 10.1016/j.jaci.2009.03.013
13. Houzelstein D, Goncalves IR, Fadden AJ, Sidhu SS, Cooper DN, Drickamer K, Leffler H, Poirier F (2004) Phylogenetic analysis of the vertebrate galectin family. Mol Biol Evol 21(7):1177-1187. doi: 10.1093/molbev/msh082
14. Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5(1):29-41. doi: 10.1038/nrc1527
15. Varki A, Schauer R (2009) Sialic acids. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York
16. Varki A (2011) Since there are PAMPs and DAMPs, there must be SAMPs? Glycan "self-associated molecular patterns" dampen innate immunity, but pathogens can mimic them. Glycobiology 21(9):1121-1124
17. Macauley MS, Paulson JC (2014) Immunology: glyco-engineering 'super-self'. Nat Chem Biol 10(1):7-8. doi: 10.1038/nchembio.1415
18. Hakomori S (1984) Tumor-associated carbohydrate antigens. Annu Rev Immunol 2:103-126. doi: 10.1146/annurev.iy.02.040184.000535
19. Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nat Rev Drug Discov 4(6):477-488. doi: 10.1038/nrd1751
20. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4(1):45-60. doi: 10.1038/nrc1251
21. Krengel U, Bousquet PA (2014) Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front Immunol 5:325. doi: 10.3389/fimmu.2014.00325
22. Kufe DW (2009) Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 9(12):874-885. doi: 10.1038/nrc2761
23. Kannagi R, Sakuma K, Miyazaki K, Lim KT, Yusa A, Yin J, Izawa M (2010) Altered expression of glycan genes in cancers induced by epigenetic silencing and tumor hypoxia: clues in the ongoing search for new tumor markers. Cancer Sci 101(3):586-593. doi: 10.1111/j.1349-7006.2009.01455.x
24. Stanley P, Schachter H, Taniguchi N (2009) N-glycans. In: Varki, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York
25. Brockhausen I, Schachter H, Stanley P (2009) O-GalNAc glycans. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York
26. Cohen M, Varki A (2010) The sialome - far more than the sum of its parts. OMICS 14(4):455-464. doi: 10.1089/omi.2009.0148
27. Varki A, Kannagi R, Toole BP (2009) Glycosylation changes in cancer. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of Glycobiology, 2nd edn. Cold Spring Harbor, New York
28. Dennis JW, Laferte S, Waghorne C, Breitman ML, Kerbel RS (1987) Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. Science 236(4801):582-585
29. Granovsky M, Fata J, Pawling J, Muller WJ, Khokha R, Dennis JW (2000) Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nat Med 6(3):306-312. doi: 10.1038/73163
30. Yoshimura M, Nishikawa A, Ihara Y, Taniguchi S, Taniguchi N (1995) Suppression of lung metastasis of B16 mouse melanoma by N-acetylglucosaminyltransferase III gene transfection. Proc Natl Acad Sci USA 92(19):8754-8758
31. Partridge EA, Le Roy C, Di Guglielmo GM, Pawling J, Cheung P, Granovsky M, Nabi IR, Wrana JL, Dennis JW (2004) Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306(5693):120-124. doi: 10.1126/science.1102109
32. Zhao YY, Takahashi M, Gu JG, Miyoshi E, Matsumoto A, Kitazume S, Taniguchi N (2008) Functional roles of N-glycans in cell signaling and cell adhesion in cancer. Cancer Sci 99(7):1304-1310. doi: 10.1111/j.1349-7006.2008.00839.x
33. Taniguchi N, Miyoshi E, Ko JH, Ikeda Y, Ihara Y (1999) Implication of N-acetylglucosaminyltransferases III and V in cancer: gene regulation and signaling mechanism. Biochim Biophys Acta 1455(2-3):287-300
34. Inamori K, Gu J, Ohira M, Kawasaki A, Nakamura Y, Nakagawa T, Kondo A, Miyoshi E, Nakagawara A, Taniguchi N (2006) High expression of N-acetylglucosaminyltransferase V in favorable neuroblastomas: involvement of its effect on apoptosis. FEBS Lett 580(2):627-632. doi: 10.1016/j.febslet.2005.12.089
35. Ihara S, Miyoshi E, Ko JH, Murata K, Nakahara S, Honke K, Dickson RB, Lin CY, Taniguchi N (2002) Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching. J Biol Chem 277(19):16960-16967. doi: 10.1074/jbc.M200673200
36. Ihara S, Miyoshi E, Nakahara S, Sakiyama H, Ihara H, Akinaga A, Honke K, Dickson RB, Lin CY, Taniguchi N (2004) Addition of beta1-6 GlcNAc branching to the oligosaccharide attached to Asn 772 in the serine protease domain of matriptase plays a pivotal role in its stability and resistance against trypsin. Glycobiology 14(2):139-146. doi: 10.1093/glycob/cwh013
37. Rambaruth ND, Dwek MV (2011) Cell surface glycan-lectin interactions in tumor metastasis. Acta Histochem 113(6):591-600. doi: 10.1016/j.acthis.2011.03.001
38. Li D, Li Y, Wu X, Li Q, Yu J, Gen J, Zhang XL (2008) Knockdown of Mgat5 inhibits breast cancer cell growth with activation of CD4+ T cells and macrophages. J Immunol 180(5):3158-3165
39. Taniguchi N, Ihara S, Saito T, Miyoshi E, Ikeda Y, Honke K (2001) Implication of GnT-V in cancer metastasis: a glycomic approach for identification of a target protein and its unique function as an angiogenic cofactor. Glycoconj J 18(11-12):859-865
40. Anugraham M, Jacob F, Nixdorf S, Everest-Dass AV, Heinzelmann-Schwarz V, Packer NH (2014) Specific glycosylation of membrane proteins in epithelial ovarian cancer cell lines: glycan structures reflect gene expression and DNA methylation status. Mol Cell Proteomics. doi: 10.1074/mcp.M113.037085
41. Zhang X, Wang Y, Qian Y, Wu X, Zhang Z, Liu X, Zhao R, Zhou L, Ruan Y, Xu J, Liu H, Ren S, Xu C, Gu J (2014) Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics. PLoS ONE 9(2):e87978. doi: 10.1371/journal.pone.0087978
42. Miwa HE, Song Y, Alvarez R, Cummings RD, Stanley P (2012) The bisecting GlcNAc in cell growth control and tumor progression. Glycoconj J 29(8-9):609-618. doi: 10.1007/s10719-012-9373-6
43. Nicoll G, Avril T, Lock K, Furukawa K, Bovin N, Crocker PR (2003) Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and -independent mechanisms. Eur J Immunol 33(6):1642-1648. doi: 10.1002/eji.200323693
44. Nores GA, Dohi T, Taniguchi M, Hakomori S (1987) Density-dependent recognition of cell surface GM3 by a certain anti-melanoma antibody, and GM3 lactone as a possible immunogen: requirements for tumor-associated antigen and immunogen. J Immunol 139(9):3171-3176
45. Miyazaki K, Ohmori K, Izawa M, Koike T, Kumamoto K, Furukawa K, Ando T, Kiso M, Yamaji T, Hashimoto Y, Suzuki A, Yoshida A, Takeuchi M, Kannagi R (2004) Loss of disialyl Lewis(a), the ligand for lymphocyte inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) associated with increased sialyl Lewis(a) expression on human colon cancers. Cancer Res 64(13):4498-4505. doi: 10.1158/0008-5472.CAN-03-3614
46. Izawa M, Kumamoto K, Mitsuoka C, Kanamori C, Kanamori A, Ohmori K, Ishida H, Nakamura S, Kurata-Miura K, Sasaki K, Nishi T, Kannagi R (2000) Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer. Cancer Res 60(5):1410-1416
47. Yusa A, Miyazaki K, Kimura N, Izawa M, Kannagi R (2010) Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewisx expression and accelerates proliferation of colon cancer cells. Cancer Res 70(10):4064-4073. doi: 10.1158/0008-5472.CAN-09-2383
48. Ju T, Lanneau GS, Gautam T, Wang Y, Xia B, Stowell SR, Willard MT, Wang W, Xia JY, Zuna RE, Laszik Z, Benbrook DM, Hanigan MH, Cummings RD (2008) Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer Res 68(6):1636-1646. doi: 10.1158/0008-5472.CAN-07-2345
49. Carrascal MA, Severino PF, Guadalupe Cabral M, Silva M, Ferreira JA, Calais F, Quinto H, Pen C, Ligeiro D, Santos LL, Dall'Olio F, Videira PA (2014) Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells. Mol Oncol 8(3):753-765. doi: 10.1016/j.molonc.2014.02.008
50. Dabelsteen E, Gao S (2005) ABO blood-group antigens in oral cancer. J Dent Res 84(1):21-28
51. Bianco T, Farmer BJ, Sage RE, Dobrovic A (2001) Loss of red cell A, B, and H antigens is frequent in myeloid malignancies. Blood 97(11):3633-3639
52. Büll C, Stoel MA, den Brok MH, Adema GJ (2014) Sialic acids sweeten a tumor's life. Cancer Res 74(12):3199-3204. doi: 10.1158/0008-5472.CAN-14-0728
53. Almaraz RT, Tian Y, Bhattarcharya R, Tan E, Chen SH, Dallas MR, Chen L, Zhang Z, Zhang H, Konstantopoulos K, Yarema KJ (2012) Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis. Mol Cell Proteomics 11(7):M112 017558. doi: 10.1074/mcp.M112.017558
54. Miyagi T, Takahashi K, Hata K, Shiozaki K, Yamaguchi K (2012) Sialidase significance for cancer progression. Glycoconj J 29(8-9):567-577. doi: 10.1007/s10719-012-9394-1
55. Hudak JE, Canham SM, Bertozzi CR (2014) Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat Chem Biol 10(1):69-75. doi: 10.1038/nchembio.1388
56. Muchmore EA, Milewski M, Varki A, Diaz S (1989) Biosynthesis of N-glycolylneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool. J Biol Chem 264(34):20216-20223
57. Shaw L, Schauer R (1988) The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol Chem Hoppe Seyler 369(6):477-486
58. Shaw L, Schauer R (1989) Detection of CMP-N-acetylneuraminic acid hydroxylase activity in fractionated mouse liver. Biochem J 263(2):355-363
59. Malykh YN, Schauer R, Shaw L (2001) N-Glycolylneuraminic acid in human tumours. Biochimie 83(7):623-634
60. Higashi H, Hirabayashi Y, Fukui Y, Naiki M, Matsumoto M, Ueda S, Kato S (1985) Characterization of N-glycolylneuraminic acid-containing gangliosides as tumor-associated Hanganutziu-Deicher antigen in human colon cancer. Cancer Res 45(8):3796-3802
61. Marquina G, Waki H, Fernandez LE, Kon K, Carr A, Valiente O, Perez R, Ando S (1996) Gangliosides expressed in human breast cancer. Cancer Res 56(22):5165-5171
62. Zhong Y, Wu Y, Li C, Tang J, Wang X, Ren G, Carr A, Perez R, Guo W (2012) N-Glycolyl GM3 ganglioside immunoexpression in oral mucosal melanomas of Chinese. Oral Dis 18(8):741-747. doi: 10.1111/j.1601-0825.2012.01939.x
63. Higashi H, Sasabe T, Fukui Y, Maru M, Kato S (1988) Detection of gangliosides as N-glycolylneuraminic acid-specific tumor-associated Hanganutziu-Deicher antigen in human retinoblastoma cells. Jpn J Cancer Res 79(8):952-956
64. Banda K, Gregg CJ, Chow R, Varki NM, Varki A (2012) Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J Biol Chem 287(34):28852-28864. doi: 10.1074/jbc.M112.364182
65. Bardor M, Nguyen DH, Diaz S, Varki A (2005) Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells. J Biol Chem 280(6):4228-4237. doi: 10.1074/jbc.M412040200
66. Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E (2003) Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA 100(21):12045-12050. doi: 10.1073/pnas.2131556100
67. Hedlund M, Tangvoranuntakul P, Takematsu H, Long JM, Housley GD, Kozutsumi Y, Suzuki A, Wynshaw-Boris A, Ryan AF, Gallo RL, Varki N, Varki A (2007) N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol 27(12):4340-4346. doi: 10.1128/MCB.00379-07
68. Yin J, Miyazaki K, Shaner RL, Merrill AH Jr, Kannagi R (2010) Altered sphingolipid metabolism induced by tumor hypoxia - new vistas in glycolipid tumor markers. FEBS Lett 584(9):1872-1878. doi: 10.1016/j.febslet.2009.11.019
69. Yin J, Hashimoto A, Izawa M, Miyazaki K, Chen GY, Takematsu H, Kozutsumi Y, Suzuki A, Furuhata K, Cheng FL, Lin CH, Sato C, Kitajima K, Kannagi R (2006) Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. Cancer Res 66(6):2937-2945. doi: 10.1158/0008-5472.CAN-05-2615
70. Zhu A, Hurst R (2002) Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation 9(6):376-381
71. Padler-Karavani V, Yu H, Cao H, Chokhawala H, Karp F, Varki N, Chen X, Varki A (2008) Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology 18(10):818-830. doi: 10.1093/glycob/cwn072
72. Padler-Karavani V, Hurtado-Ziola N, Pu M, Yu H, Huang S, Muthana S, Chokhawala HA, Cao H, Secrest P, Friedmann-Morvinski D, Singer O, Ghaderi D, Verma IM, Liu YT, Messer K, Chen X, Varki A, Schwab R (2011) Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. Cancer Res 71(9):3352-3363. doi: 10.1158/0008-5472.CAN-10-4102
73. Samraj AN, Laubli H, Varki N, Varki A (2014) Involvement of a non-human sialic Acid in human cancer. Front Oncol 4:33. doi: 10.3389/fonc.2014.00033
74. Amon R, Reuven EM, Leviatan Ben-Arye S, Padler-Karavani V (2014) Glycans in immune recognition and response. Carbohydr Res 389:115-122. doi: 10.1016/j.carres.2014.02.004
75. Pearce OM, Laubli H, Verhagen A, Secrest P, Zhang J, Varki NM, Crocker PR, Bui JD, Varki A (2014) Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies. Proc Natl Acad Sci USA 111(16):5998-6003. doi: 10.1073/pnas.1209067111
76. Hedlund M, Padler-Karavani V, Varki NM, Varki A (2008) Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression. Proc Natl Acad Sci USA 105(48):18936-18941. doi: 10.1073/pnas.0803943105
77. Marth JD, Grewal PK (2008) Mammalian glycosylation in immunity. Nat Rev Immunol 8(11):874-887. doi: 10.1038/nri2417
78. van Kooyk Y, Rabinovich GA (2008) Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol 9(6):593-601. doi: 10.1038/ni.f.203
79. von Gunten S, Shoenfeld Y, Blank M, Branch DR, Vassilev T, Käsermann F, Bayry J, Kaveri S, Simon HU (2014) IVIG pluripotency and the concept of Fc-sialylation: challenges to the scientist. Nat Rev Immunol 14(5):349. doi: 10.1038/nri3401-c1
80. Varki A (2007) Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 446(7139):1023-1029. doi: 10.1038/nature05816
81. Rabinovich GA, Croci DO (2012) Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 36(3):322-335. doi: 10.1016/j.immuni.2012.03.004
82. Geijtenbeek TB, Gringhuis SI (2009) Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9(7):465-479. doi: 10.1038/nri2569
83. von Gunten S, Bochner BS (2008) Basic and clinical immunology of Siglecs. Ann N Y Acad Sci 1143:61-82. doi: 10.1196/annals.1443.011
84. Zhuo Y, Bellis SL (2011) Emerging role of alpha2,6-sialic acid as a negative regulator of galectin binding and function. J Biol Chem 286(8):5935-5941. doi: 10.1074/jbc.R110.191429
85. Jandus C, Boligan KF, Chijioke O, Liu H, Dahlhaus M, Demoulins T, Schneider C, Wehrli M, Hunger RE, Baerlocher GM, Simon HU, Romero P, Munz C, von Gunten S (2014) Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Invest 124(4):1810-1820. doi: 10.1172/JCI65899
86. Kawasaki Y, Ito A, Withers DA, Taima T, Kakoi N, Saito S, Arai Y (2010) Ganglioside DSGb5, preferred ligand for Siglec-7, inhibits NK cell cytotoxicity against renal cell carcinoma cells. Glycobiology 20(11):1373-1379. doi: 10.1093/glycob/cwq116
87. Cohen M, Elkabets M, Perlmutter M, Porgador A, Voronov E, Apte RN, Lichtenstein RG (2010) Sialylation of 3-methylcholanthrene-induced fibrosarcoma determines antitumor immune responses during immunoediting. J Immunol 185(10):5869-5878. doi: 10.4049/jimmunol.1001635
88. Tsuboi S, Sutoh M, Hatakeyama S, Hiraoka N, Habuchi T, Horikawa Y, Hashimoto Y, Yoneyama T, Mori K, Koie T, Nakamura T, Saitoh H, Yamaya K, Funyu T, Fukuda M, Ohyama C (2011) A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J 30(15):3173-3185. doi: 10.1038/emboj.2011.215
89. Kim YJ, Borsig L, Varki NM, Varki A (1998) P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci USA 95(16):9325-9330
90. Stone JP, Wagner DD (1993) P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. J Clin Invest 92(2):804-813. doi: 10.1172/JCI116654
91. Garcia J, Callewaert N, Borsig L (2007) P-selectin mediates metastatic progression through binding to sulfatides on tumor cells. Glycobiology 17(2):185-196. doi: 10.1093/glycob/cwl059
92. Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A (2001) Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA 98(6):3352-3357. doi: 10.1073/pnas.061615598
93. Nieswandt B, Hafner M, Echtenacher B, Mannel DN (1999) Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 59(6):1295-1300
94. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirouskova M, Degen JL (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105(1):178-185. doi: 10.1182/blood-2004-06-2272
95. Kopp HG, Placke T, Salih HR (2009) Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res 69(19):7775-7783. doi: 10.1158/0008-5472.CAN-09-2123
96. Crespo HJ, Lau JT, Videira PA (2013) Dendritic cells: a spot on sialic acid. Front Immunol 4:491. doi: 10.3389/fimmu.2013.00491
97. Napoletano C, Rughetti A, Agervig Tarp MP, Coleman J, Bennett EP, Picco G, Sale P, Denda-Nagai K, Irimura T, Mandel U, Clausen H, Frati L, Taylor-Papadimitriou J, Burchell J, Nuti M (2007) Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. Cancer Res 67(17):8358-8367. doi: 10.1158/0008-5472.CAN-07-1035
98. Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Saeland E, van Kooyk Y (2011) Tumour-associated glycan modifications of antigen enhance MGL2 dependent uptake and MHC class I restricted CD8 T cell responses. Int J Cancer 128(6):1371-1383. doi: 10.1002/ijc.25458
99. Nonaka M, Ma BY, Murai R, Nakamura N, Baba M, Kawasaki N, Hodohara K, Asano S, Kawasaki T (2008) Glycosylation-dependent interactions of C-type lectin DC-SIGN with colorectal tumor-associated Lewis glycans impair the function and differentiation of monocyte-derived dendritic cells. J Immunol 180(5):3347-3356
100. Fedarko NS, Fohr B, Robey PG, Young MF, Fisher LW (2000) Factor H binding to bone sialoprotein and osteopontin enables tumor cell evasion of complement-mediated attack. J Biol Chem 275(22):16666-16672. doi: 10.1074/jbc.M001123200
101. Shi WX, Chammas R, Varki NM, Powell L, Varki A (1996) Sialic acid 9-O-acetylation on murine erythroleukemia cells affects complement activation, binding to I-type lectins, and tissue homing. J Biol Chem 271(49):31526-31532
102. Ajona D, Castano Z, Garayoa M, Zudaire E, Pajares MJ, Martinez A, Cuttitta F, Montuenga LM, Pio R (2004) Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement. Cancer Res 64(17):6310-6318. doi: 10.1158/0008-5472.CAN-03-2328
103. Crocker PR, Paulson JC, Varki A (2007) Siglecs and their roles in the immune system. Nat Rev Immunol 7(4):255-266. doi: 10.1038/nri2056
104. Crocker PR, Redelinghuys P (2008) Siglecs as positive and negative regulators of the immune system. Biochem Soc Trans 36(Pt 6):1467-1471. doi: 10.1042/BST0361467
105. Jandus C, Simon HU, von Gunten S (2011) Targeting siglecs - a novel pharmacological strategy for immuno- and glycotherapy. Biochem Pharmacol 82(4):323-332. doi: 10.1016/j.bcp.2011.05.018
106. Cao H, Crocker PR (2011) Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation? Immunology 132(1):18-26. doi: 10.1111/j.1365-2567.2010.03368.x
107. Macauley MS, Crocker PR, Paulson JC (2014) Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 14(10):653-666. doi: 10.1038/nri3737
108. von Gunten S, Simon HU (2006) Sialic acid binding immunoglobulin-like lectins may regulate innate immune responses by modulating the life span of granulocytes. FASEB J 20(6):601-605. doi: 10.1096/fj.05-5401hyp
109. Crocker PR, McMillan SJ, Richards HE (2012) CD33-related siglecs as potential modulators of inflammatory responses. Ann N Y Acad Sci 1253:102-111. doi: 10.1111/j.1749-6632.2011.06449.x
110. Nutku E, Aizawa H, Hudson SA, Bochner BS (2003) Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis. Blood 101(12):5014-5020. doi: 10.1182/blood-2002-10-3058
111. von Gunten S, Yousefi S, Seitz M, Jakob SM, Schaffner T, Seger R, Takala J, Villiger PM, Simon HU (2005) Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment. Blood 106(4):1423-1431. doi: 10.1182/blood-2004-10-4112
112. Mitsuki M, Nara K, Yamaji T, Enomoto A, Kanno M, Yamaguchi Y, Yamada A, Waguri S, Hashimoto Y (2010) Siglec-7 mediates nonapoptotic cell death independently of its immunoreceptor tyrosine-based inhibitory motifs in monocytic cell line U937. Glycobiology 20(3):395-402. doi: 10.1093/glycob/cwp195
113. von Gunten S, Jakob SM, Geering B, Takala J, Simon HU (2009) Different patterns of Siglec-9-mediated neutrophil death responses in septic shock. Shock 32(4):386-392. doi: 10.1097/SHK.0b013e3181a1bc98
114. von Gunten S, Simon HU (2007) Autophagic-like cell death in neutrophils induced by autoantibodies. Autophagy 3(1):67-68
115. von Gunten S, Schaub A, Vogel M, Stadler BM, Miescher S, Simon HU (2006) Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations. Blood 108(13):4255-4259. doi: 10.1182/blood-2006-05-021568
116. von Gunten S, Vogel M, Schaub A, Stadler BM, Miescher S, Crocker PR, Simon HU (2007) Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies. J Allergy Clin Immunol 119(4):1005-1011. doi: 10.1016/j.jaci.2007.01.023
117. Schaub A, von Gunten S, Vogel M, Wymann S, Ruegsegger M, Stadler BM, Spycher M, Simon HU, Miescher S (2011) Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes. Allergy 66(8):1030-1037. doi: 10.1111/j.1398-9995.2011.02579.x
118. von Gunten S, Simon HU (2012) Granulocyte death regulation by naturally occurring autoantibodies. Adv Exp Med Biol 750:157-172. doi: 10.1007/978-1-4614-3461-0-12
119. von Gunten S, Simon HU (2010) Cell death modulation by intravenous immunoglobulin. J Clin Immunol 30(Suppl 1):S24-S30. doi: 10.1007/s10875-010-9411-8
120. von Gunten S, Wehrli M, Simon HU (2013) Cell death in immune thrombocytopenia: novel insights and perspectives. Semin Hematol 50(Suppl 1):S109-S115. doi: 10.1053/j.seminhematol.2013.03.016
121. Chen GY, Tang J, Zheng P, Liu Y (2009) CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323(5922):1722-1725. doi: 10.1126/science.1168988
122. Läubli H, Pearce OM, Schwarz F, Siddiqui SS, Deng L, Stanczak MA, Deng L, Verhagen A, Secrest P, Lusk C, Schwartz AG, Varki NM, Bui JD, Varki A (2014) Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc Natl Acad Sci USA. doi: 10.1073/pnas.1409580111
123. Miyazaki K, Sakuma K, Kawamura YI, Izawa M, Ohmori K, Mitsuki M, Yamaji T, Hashimoto Y, Suzuki A, Saito Y, Dohi T, Kannagi R (2012) Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and -9. J Immunol 188(9):4690-4700. doi: 10.4049/jimmunol.1100605
124. Tomioka Y, Morimatsu M, Nishijima K, Usui T, Yamamoto S, Suyama H, Ozaki K, Ito T, Ono E (2014) A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice. Biochem Biophys Res Commun 450(1):532-537. doi: 10.1016/j.bbrc.2014.06.009
125. Ohta M, Ishida A, Toda M, Akita K, Inoue M, Yamashita K, Watanabe M, Murata T, Usui T, Nakada H (2010) Immunomodulation of monocyte-derived dendritic cells through ligation of tumor-produced mucins to Siglec-9. Biochem Biophys Res Commun 402(4):663-669. doi: 10.1016/j.bbrc.2010.10.079
126. Toda M, Akita K, Inoue M, Taketani S, Nakada H (2008) Down-modulation of B cell signal transduction by ligation of mucins to CD22. Biochem Biophys Res Commun 372(1):45-50. doi: 10.1016/j.bbrc.2008.04.175
127. Toda M, Hisano R, Yurugi H, Akita K, Maruyama K, Inoue M, Adachi T, Tsubata T, Nakada H (2009) Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells. Biochem J 417(3):673-683. doi: 10.1042/BJ20081241
128. Mitic N, Milutinovic B, Jankovic M (2012) Assessment of sialic acid diversity in cancer- and non-cancer related CA125 antigen using sialic acid-binding Ig-like lectins (Siglecs). Dis Markers 32(3):187-194. doi: 10.3233/DMA-2011-0872
129. Belisle JA, Horibata S, Jennifer GA, Petrie S, Kapur A, Andre S, Gabius HJ, Rancourt C, Connor J, Paulson JC, Patankar MS (2010) Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol Cancer 9:118. doi: 10.1186/1476-4598-9-118
130. Sabit I, Hashimoto N, Matsumoto Y, Yamaji T, Furukawa K, Furukawa K (2013) Binding of a sialic acid-recognizing lectin Siglec-9 modulates adhesion dynamics of cancer cells via calpain-mediated protein degradation. J Biol Chem 288(49):35417-35427. doi: 10.1074/jbc.M113.513192
131. Tanida S, Akita K, Ishida A, Mori Y, Toda M, Inoue M, Ohta M, Yashiro M, Sawada T, Hirakawa K, Nakada H (2013) Binding of the sialic acid-binding lectin, Siglec-9, to the membrane mucin, MUC1, induces recruitment of beta-catenin and subsequent cell growth. J Biol Chem 288(44):31842-31852. doi: 10.1074/jbc.M113.471318
132. Aalto K, Autio A, Kiss EA, Elima K, Nymalm Y, Veres TZ, Marttila-Ichihara F, Elovaara H, Saanijoki T, Crocker PR, Maksimow M, Bligt E, Salminen TA, Salmi M, Roivainen A, Jalkanen S (2011) Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer. Blood 118(13):3725-3733. doi: 10.1182/blood-2010-09-311076
133. Kivi E, Elima K, Aalto K, Nymalm Y, Auvinen K, Koivunen E, Otto DM, Crocker PR, Salminen TA, Salmi M, Jalkanen S (2009) Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate. Blood 114(26):5385-5392. doi: 10.1182/blood-2009-04-219253
134. Kiwamoto T, Kawasaki N, Paulson JC, Bochner BS (2012) Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol Ther 135(3):327-336. doi: 10.1016/j.pharmthera.2012.06.005
135. O'Reilly MK, Paulson JC (2009) Siglecs as targets for therapy in immune-cell-mediated disease. Trends Pharmacol Sci 30(5):240-248. doi: 10.1016/j.tips.2009.02.005
136. Chen WC, Sigal DS, Saven A, Paulson JC (2012) Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22. Leuk Lymphoma 53(2):208-210. doi: 10.3109/10428194.2011.604755
137. Läubli H, Borsig L (2010) Selectins promote tumor metastasis. Semin Cancer Biol 20(3):169-177. doi: 10.1016/j.semcancer.2010.04.005
138. Girard JP, Moussion C, Forster R (2012) HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol 12(11):762-773. doi: 10.1038/nri3298
139. Blagoveshchenskaya AD, Norcott JP, Cutler DF (1998) Lysosomal targeting of P-selectin is mediated by a novel sequence within its cytoplasmic tail. J Biol Chem 273(5):2729-2737
140. Sanada H, Midorikawa S, Yatabe J, Yatabe MS, Katoh T, Baba T, Hashimoto S, Watanabe T (2005) Elevation of serum soluble E- and P-selectin in patients with hypertension is reversed by benidipine, a long-acting calcium channel blocker. Hypertens Res 28(11):871-878. doi: 10.1291/hypres.28.871
141. Kisucka J, Chauhan AK, Zhao BQ, Patten IS, Yesilaltay A, Krieger M, Wagner DD (2009) Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 113(23):6015-6022. doi: 10.1182/blood-2008-10-186650
142. Ay C, Simanek R, Vormittag R, Dunkler D, Alguel G, Koder S, Kornek G, Marosi C, Wagner O, Zielinski C, Pabinger I (2008) High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 112(7):2703-2708. doi: 10.1182/blood-2008-02-142422
143. Kawashima H, Fukuda M (2012) Sulfated glycans control lymphocyte homing. Ann N Y Acad Sci 1253:112-121. doi: 10.1111/j.1749-6632.2011.06356.x
144. Krause T, Turner GA (1999) Are selectins involved in metastasis? Clin Exp Metastasis 17(3):183-192
145. Hoos A, Protsyuk D, Borsig L (2014) Metastatic growth progression caused by PSGL-1-mediated recruitment of monocytes to metastatic sites. Cancer Res 74(3):695-704. doi: 10.1158/0008-5472.CAN-13-0946
146. Borsig L, Wong R, Hynes RO, Varki NM, Varki A (2002) Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA 99(4):2193-2198. doi: 10.1073/pnas.261704098
147. Heidemann F, Schildt A, Schmid K, Bruns OT, Riecken K, Jung C, Ittrich H, Wicklein D, Reimer R, Fehse B, Heeren J, Luers G, Schumacher U, Heine M (2014) Selectins mediate small cell lung cancer systemic metastasis. PLoS ONE 9(4):e92327. doi: 10.1371/journal.pone.0092327
148. Läubli H, Stevenson JL, Varki A, Varki NM, Borsig L (2006) L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res 66(3):1536-1542. doi: 10.1158/0008-5472.CAN-05-3121
149. Prinetti A, Aureli M, Illuzzi G, Prioni S, Nocco V, Scandroglio F, Gagliano N, Tredici G, Rodriguez-Menendez V, Chigorno V, Sonnino S (2010) GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells. Glycobiology 20(1):62-77. doi: 10.1093/glycob/cwp143
150. Prinetti A, Cao T, Illuzzi G, Prioni S, Aureli M, Gagliano N, Tredici G, Rodriguez-Menendez V, Chigorno V, Sonnino S (2011) A glycosphingolipid/caveolin-1 signaling complex inhibits motility of human ovarian carcinoma cells. J Biol Chem 286(47):40900-40910. doi: 10.1074/jbc.M111.286146
151. Tringali C, Lupo B, Cirillo F, Papini N, Anastasia L, Lamorte G, Colombi P, Bresciani R, Monti E, Tettamanti G, Venerando B (2009) Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3. Cell Death Differ 16(1):164-174. doi: 10.1038/cdd.2008.141
152. Handa K, Hakomori SI (2012) Carbohydrate to carbohydrate interaction in development process and cancer progression. Glycoconj J 29(8-9):627-637. doi: 10.1007/s10719-012-9380-7
153. Potapenko M, Shurin GV, de Leon J (2007) Gangliosides as immunomodulators. Adv Exp Med Biol 601:195-203
154. Varki A, Freeze HH (2009) Glycans in acquired human diseases. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor, New York
155. Casadesus AV, Fernandez-Marrero Y, Clavell M, Gomez JA, Hernandez T, Moreno E, Lopez-Requena A (2013) A shift from N-glycolyl- to N-acetyl-sialic acid in the GM3 ganglioside impairs tumor development in mouse lymphocytic leukemia cells. Glycoconj J 30(7):687-699. doi: 10.1007/s10719-013-9473-y
156. Gabri MR, Otero LL, Gomez DE, Alonso DF (2009) Exogenous incorporation of Neugc-rich mucin augments N-glycolyl sialic acid content and promotes malignant phenotype in mouse tumor cell lines. J Exp Clin Cancer Res 28:146. doi: 10.1186/1756-9966-28-146
157. Segatori VI, Vazquez AM, Gomez DE, Gabri MR, Alonso DF (2012) Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N-glycolyl-containing gangliosides, with or without chemotherapy in a mouse model of non-small cell lung cancer. Front Oncol 2:160. doi: 10.3389/fonc.2012.00160
158. Segatori VI, Otero LL, Fernandez LE, Gomez DE, Alonso DF, Gabri MR (2012) Antitumor protection by NGcGM3/VSSP vaccine against transfected B16 mouse melanoma cells overexpressing N-glycolylated gangliosides. Vivo 26(4):609-617
159. Labrada M, Clavell M, Bebelagua Y, Leon J, Alonso DF, Gabri MR, Veloso RC, Verez V, Fernandez LE (2010) Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy. Expert Opin Biol Ther 10(2):153-162. doi: 10.1517/14712590903443084
160. de Leon J, Fernandez A, Clavell M, Labrada M, Bebelagua Y, Mesa C, Fernandez LE (2008) Differential influence of the tumour-specific non-human sialic acid containing GM3 ganglioside on CD4+ CD25- effector and naturally occurring CD4+ CD25+ regulatory T cells function. Int Immunol 20(4):591-600. doi: 10.1093/intimm/dxn018
161. de Leon J, Fernandez A, Mesa C, Clavel M, Fernandez LE (2006) Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells. Cancer Immunol Immunother 55(4):443-450. doi: 10.1007/s00262-005-0041-6
162. Blanco R, Blanco D, Quintana Y, Escobar X, Rengifo CE, Osorio M, Gutierrez Z, Lamadrid J, Cedeno M, Frometa M, Carr A, Rengifo E (2013) Immunoreactivity of the 14F7 Mab raised against N-Glycolyl GM3 ganglioside in primary lymphoid tumors and lymph node metastasis. Pathol Res Int 2013:920972. doi: 10.1155/2013/920972
163. Blanco R, Rengifo E, Cedeno M, Rengifo CE, Alonso DF, Carr A (2011) Immunoreactivity of the 14F7 Mab raised against N-glycolyl GM3 ganglioside in epithelial malignant tumors from digestive system. ISRN Gastroenterol 2011:645641. doi: 10.5402/2011/645641
164. Blanco RQ, Cedeño M, Rengifo CE, Frómeta M, Ríos M, Rengifo E, Carr A (2013) Tissue reactivity of the 14F7 Mab raised against N-glycolyl GM3 ganglioside in tumors of neuroectodermal, mesodermal, and epithelial origin. J Biomarkers 2013:9. doi: 10.1155/2013/602417
165. Hayashi N, Chiba H, Kuronuma K, Go S, Hasegawa Y, Takahashi M, Gasa S, Watanabe A, Hasegawa T, Kuroki Y, Inokuchi J, Takahashi H (2013) Detection of N-glycosylated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody. Cancer Sci 104(1):43-47. doi: 10.1111/cas.12027
166. Vazquez AM, Perez A, Hernandez AM, Macias A, Alfonso M, Bombino G, Perez R (1998) Syngeneic anti-idiotypic monoclonal antibodies to an anti-NeuGc-containing ganglioside monoclonal antibody. Hybridoma 17(6):527-534
167. Hernandez AM, Toledo D, Martinez D, Grinan T, Brito V, Macias A, Alfonso S, Rondon T, Suarez E, Vazquez AM, Perez R (2008) Characterization of the antibody response against NeuGcGM3 ganglioside elicited in non-small cell lung cancer patients immunized with an anti-idiotype antibody. J Immunol 181(9):6625-6634
168. Alfonso S, Valdes-Zayas A, Santiesteban ER, Flores YI, Areces F, Hernandez M, Viada C, Mendoza IC, Guerra PP, Garcia E, Ortiz RA, de la Torre AV, Cepeda M, Perez K, Chong E, Hernandez AM, Toledo D, Gonzalez Z, Mazorra Z, Crombet T, Perez R, Vazquez AM, Macias AE (2014) A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small-cell-lung cancer patients. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-13-1674
169. Fernandez LE, Gabri MR, Guthmann MD, Gomez RE, Gold S, Fainboim L, Gomez DE, Alonso DF (2010) NGcGM3 ganglioside: a privileged target for cancer vaccines. Clin Dev Immunol 2010:814397. doi: 10.1155/2010/814397
170. Estevez F, Carr A, Solorzano L, Valiente O, Mesa C, Barroso O, Sierra GV, Fernandez LE (1999) Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP). Vaccine 18(1-2):190-197
171. Mulens V, de la Torre A, Marinello P, Rodriguez R, Cardoso J, Diaz R, O'Farrill M, Macias A, Viada C, Saurez G, Carr A, Crombet T, Mazorra Z, Perez R, Fernandez LE (2010) Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: results from a controlled study in metastatic breast cancer patients. Hum Vaccin 6(9). doi:10.4161.hv.6.9.12571
172. Osorio M, Gracia E, Reigosa E, Hernandez J, de la Torre A, Saurez G, Perez K, Viada C, Cepeda M, Carr A, Avila Y, Rodriguez M, Fernandez LE (2012) Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma. Cancer Manag Res 4:341-345. doi: 10.2147/CMAR.S22617
173. Meezan E, Wu HC, Black PH, Robbins PW (1969) Comparative studies on the carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. II. Separation of glycoproteins and glycopeptides by sephadex chromatography. Biochemistry 8(6):2518-2524
174. Kieber-Emmons T, Saha S, Pashov A, Monzavi-Karbassi B, Murali R (2014) Carbohydrate-mimetic peptides for pan anti-tumor responses. Front Immunol 5:308. doi: 10.3389/fimmu.2014.00308
175. Shirota K, Kato Y, Irimura T, Kondo H, Sugiyama Y (2001) Anti-metastatic effect of the sialyl Lewis-X analog GSC-150 on the human colon carcinoma derived cell line KM12-HX in the mouse. Biol Pharm Bull 24(3):316-319