Applications of Antibody-Lectin Sandwich Arrays (ALSA) to Pancreatic Cancer Diagnostics and Drug Discovery

  • Yi-Mi Wu
  • Brian B. HaabEmail author


A growing body of research in recent years is establishing the importance of glycosylation in cancer. Several types of cancer, especially epithelial carcinomas such as pancreatic cancer, commonly display particular carbohydrate alterations that have potential functional roles in cancer progression. New analytical tools are providing enhanced opportunities for studying glycans in cancer. One such tool is the antibody-lectin sandwich array (ALSA). ALSA complements existing glycobiology methods by offering a unique set of capabilities, such as reproducible detection of glycans on specific proteins, sensitive detection directly from biological samples, multiplexed analysis of both core protein and glycan levels, and low-volume, high-throughput sample processing. Using this tool, one may characterize glycan variation in populations, identify glycan changes on specific proteins in model systems, or characterize protein carriers of specific glycans. These types of experiments will be especially useful in pancreatic cancer research in studies to develop biomarkers and to define therapeutic targets.


Pancreatic Cancer Sialic Acid Glycan Structure Protein Glycosylation Lewis Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank the NCI (4R33CA122890) and the Van Andel Institute for their support of this work.


  1. Alper J (2001) Searching for medicine’s sweet spot. Science 291:2338–2343PubMedCrossRefGoogle Scholar
  2. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867PubMedCrossRefGoogle Scholar
  3. Andrianifahanana M, Moniaux N, Batra SK (2006) Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases. Biochim Biophys Acta 1765:189–222PubMedGoogle Scholar
  4. Apweiler R, Hermjakob H, Sharon N (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta 1473:4–8PubMedGoogle Scholar
  5. Babiker AA, Nilsson B, Ronquist G et al (2005) Transfer of functional prostasomal CD59 of metastatic prostatic cancer cell origin protects cells against complement attack. Prostate 62:105–114PubMedCrossRefGoogle Scholar
  6. Becker DJ, Lowe JB (2003) Fucose: biosynthesis and biological function in mammals. Glycobiology 13:41R–53RPubMedCrossRefGoogle Scholar
  7. Biancone L, Araki M, Araki K et al (1996) Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med 183:581–587PubMedCrossRefGoogle Scholar
  8. Blixt O, Head S, Mondala T et al (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci USA 101:17033–17038PubMedCrossRefGoogle Scholar
  9. Brewer CF, Miceli MC, Baum LG (2002) Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. Curr Opin Struct Biol 12:616–623PubMedCrossRefGoogle Scholar
  10. Brockhausen I (2000) O-linked chain glycosyltransferases. Methods Mol Biol 125:273–293PubMedGoogle Scholar
  11. Brockhausen I (2006) Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep 7:599–604PubMedCrossRefGoogle Scholar
  12. Brown JR, Fuster MM, Li R et al (2006) A disaccharide-based inhibitor of glycosylation attenuates metastatic tumor cell dissemination. Clin Cancer Res 12:2894–2901PubMedCrossRefGoogle Scholar
  13. Burchell JM, Mungul A, Taylor-Papadimitriou J (2001) O-linked glycosylation in the mammary gland: changes that occur during malignancy. J Mammary Gland Biol Neoplasia 6:355–364PubMedCrossRefGoogle Scholar
  14. Cabrera PV, Amano M, Mitoma J et al (2006) Haploinsufficiency of C2GnT-I glycosyltransferase renders T lymphoma cells resistant to cell death. Blood 108:2399–2406PubMedCrossRefGoogle Scholar
  15. Campbell BJ, Finnie IA, Hounsell EF et al (1995) Direct demonstration of increased expression of Thomsen−Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. J Clin Invest 95:571–576PubMedCrossRefGoogle Scholar
  16. Campbell BJ, Yu LG, Rhodes JM (2001) Altered glycosylation in inflammatory bowel disease: a possible role in cancer development. Glycoconj J 18:851–858PubMedCrossRefGoogle Scholar
  17. Chen S, LaRoche T, Hamelinck D et al (2007) Multiplexed analysis of glycan variation on native proteins captured by antibody microarrays. Nat Methods 4:437–444PubMedCrossRefGoogle Scholar
  18. Chiricolo M, Malagolini N, Bonfiglioli S et al (2006) Phenotypic changes induced by expression of beta-galactoside alpha2,6 sialyltransferase I in the human colon cancer cell line SW948. Glycobiology 16:146–154PubMedCrossRefGoogle Scholar
  19. Cooper DN (2002) Galectinomics: finding themes in complexity. Biochim Biophys Acta 1572:209–231PubMedGoogle Scholar
  20. Dabelsteen E, Gao S (2005) ABO blood-group antigens in oral cancer. J Dent Res 84:21–28PubMedCrossRefGoogle Scholar
  21. Dall’Olio F, Chiricolo M (2001) Sialyltransferases in cancer. Glycoconj J 18:841–850PubMedCrossRefGoogle Scholar
  22. Dalziel M, Whitehouse C, McFarlane I et al (2001) The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1. J Biol Chem 276:11007–11015PubMedCrossRefGoogle Scholar
  23. Demetriou M, Granovsky M, Quaggin S et al (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733–739PubMedCrossRefGoogle Scholar
  24. Dennis JW (1986) Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. Cancer Res 46:5131–5136PubMedGoogle Scholar
  25. Dennis J, Waller C, Timpl R et al (1982) Surface sialic acid reduces attachment of metastatic tumour cells to collagen type IV and fibronectin. Nature 300:274–276PubMedCrossRefGoogle Scholar
  26. Dennis JW, Granovsky M, Warren CE (1999) Glycoprotein glycosylation and cancer progression. Biochim Biophys Acta 1473:21–34PubMedGoogle Scholar
  27. Dorling PR, Huxtable CR, Colegate SM (1980) Inhibition of lysosomal alpha-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens. Biochem J 191:649–651PubMedGoogle Scholar
  28. Dricu A, Carlberg M, Wang M et al (1997) Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res 57:543–548PubMedGoogle Scholar
  29. Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation−potential for therapeutics and diagnostics. Nat Rev Drug Discov 4:477–488PubMedCrossRefGoogle Scholar
  30. Elbein AD (1987) Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu Rev Biochem 56:497–534PubMedCrossRefGoogle Scholar
  31. Ellgaard L, Helenius A (2001) ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 13:431–437PubMedCrossRefGoogle Scholar
  32. Ferrone CR, Finkelstein DM, Thayer SP et al (2006) Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol 24:2897–2902PubMedCrossRefGoogle Scholar
  33. Forrester S, Kuick R, Hung KE et al (2007) Low-volume, high-throughput sandwich immunoassays for profiling plasma proteins in mice: identification of early-stage systemic inflammation in a mouse model of intestinal cancer. Molecular Oncology 1:216–225PubMedCrossRefGoogle Scholar
  34. Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244PubMedGoogle Scholar
  35. Fukushima K, Hirota M, Terasaki PI et al (1984) Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res 44:5279–5285PubMedGoogle Scholar
  36. Fuster MM, Esko JD (2005) The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5:526–542PubMedCrossRefGoogle Scholar
  37. Fuster MM, Brown JR, Wang L et al (2003) A disaccharide precursor of sialyl Lewis X inhibits metastatic potential of tumor cells. Cancer Res 63:2775–2781PubMedGoogle Scholar
  38. Gao WM, Kuick R, Orchekowski RP et al (2005) Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis. BMC Cancer 5:110PubMedCrossRefGoogle Scholar
  39. Gendler SJ, Spicer AP (1995) Epithelial mucin genes. Annu Rev Physiol 57:607–634PubMedCrossRefGoogle Scholar
  40. Gilewski T, Ragupathi G, Bhuta S et al (2001) Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial. Proc Natl Acad Sci USA 98:3270–3275PubMedCrossRefGoogle Scholar
  41. Gilewski TA, Ragupathi G, Dickler M et al (2007) Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21. Clin Cancer Res 13:2977–2985PubMedCrossRefGoogle Scholar
  42. Glinsky VV, Glinsky GV, Rittenhouse-Olson K et al (2001) The role of Thomsen−Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer Res 61:4851–4857PubMedGoogle Scholar
  43. Goetz JA, Mechref Y, Kang P et al (2008) Glycomic profiling of invasive and non-invasive breast cancer cells. Glycoconj J 26:117–131PubMedCrossRefGoogle Scholar
  44. Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 33:266–270PubMedCrossRefGoogle Scholar
  45. Gourevitch MM, von Mensdorff-Pouilly S, Litvinov SV et al (1995) Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients. Br J Cancer 72:934–938PubMedGoogle Scholar
  46. Granovsky M, Fata J, Pawling J et al (2000) Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nat Med 6:306–312PubMedCrossRefGoogle Scholar
  47. Haab BB, Dunham MJ, Brown PO (2001) Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol 2:Research0004Google Scholar
  48. Hagisawa S, Ohyama C, Takahashi T et al (2005) Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression. Glycobiology 15:1016–1024PubMedCrossRefGoogle Scholar
  49. Haltiwanger RS, Lowe JB (2004) Role of glycosylation in development. Annu Rev Biochem 73:491–537PubMedCrossRefGoogle Scholar
  50. Hang HC, Bertozzi CR (2005) The chemistry and biology of mucin-type O-linked glycosylation. Bioorg Med Chem 13:5021–5034PubMedCrossRefGoogle Scholar
  51. Hanisch FG, Hanski C, Hasegawa A (1992) Sialyl Lewis(x) antigen as defined by monoclonal antibody AM-3 is a marker of dysplasia in the colonic adenoma-carcinoma sequence. Cancer Res 52:3138–3144PubMedGoogle Scholar
  52. Higashi N, Fujioka K, Denda-Nagai K et al (2002) The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J Biol Chem 277:20686–20693PubMedCrossRefGoogle Scholar
  53. Hoff SD, Matsushita Y, Ota DM et al (1989) Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. Cancer Res 49:6883–6888PubMedGoogle Scholar
  54. Hollingsworth MA, Swanson BJ (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4:45–60PubMedCrossRefGoogle Scholar
  55. Houzelstein D, Goncalves IR, Fadden AJ et al (2004) Phylogenetic analysis of the vertebrate galectin family. Mol Biol Evol 21:1177–1187PubMedCrossRefGoogle Scholar
  56. Huang MC, Chen HY, Huang HC et al (2006) C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells. Oncogene 25:3267–3276PubMedCrossRefGoogle Scholar
  57. Humphries MJ, Matsumoto K, White SL et al (1986) Inhibition of experimental metastasis by castanospermine in mice: blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. Cancer Res 46:5215–5222PubMedGoogle Scholar
  58. Irimura T, Gonzalez R, Nicolson GL (1981) Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties. Cancer Res 41:3411–3418PubMedGoogle Scholar
  59. Iwai K, Ishikura H, Kaji M et al (1993) Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium. Int J Cancer 54:972–977PubMedCrossRefGoogle Scholar
  60. Izawa M, Kumamoto K, Mitsuoka C et al (2000) Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer. Cancer Res 60:1410–1416PubMedGoogle Scholar
  61. Johnsen AK, Templeton DJ, Sy M et al (1999) Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis. J Immunol 163:4224–4231PubMedGoogle Scholar
  62. Kakiuchi Y, Tsuji S, Tsujii M et al (2002) Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Cancer Res 62:1567–1572PubMedGoogle Scholar
  63. Kannagi R (1997) Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj J 14:577–584PubMedCrossRefGoogle Scholar
  64. Kawarada Y, Ishikura H, Kishimoto T et al (2000) The role of sialylated Lewis antigens on hematogenous metastases of human pancreas carcinoma cell lines in vivo. Pathol Res Pract 196:259–263PubMedGoogle Scholar
  65. Kikuchi J, Shinohara H, Nonomura C et al (2005) Not core 2 beta 1,6-N-acetylglucosaminyltransferase-2 or -3 but -1 regulates sialyl-Lewis x expression in human precursor B cells. Glycobiology 15:271–280PubMedCrossRefGoogle Scholar
  66. Kim YS, Itzkowitz SH, Yuan M et al (1988) Lex and Ley antigen expression in human pancreatic cancer. Cancer Res 48:475–482PubMedGoogle Scholar
  67. Kim YS, Gum J Jr, Brockhausen I (1996) Mucin glycoproteins in neoplasia. Glycoconj J 13:693–707PubMedCrossRefGoogle Scholar
  68. Kishimoto T, Ishikura H, Kimura C et al (1996) Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen. Int J Cancer 69:290–294PubMedCrossRefGoogle Scholar
  69. Kjeldsen T, Clausen H, Hirohashi S et al (1988) Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2—6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope. Cancer Res 48:2214–2220PubMedGoogle Scholar
  70. Kobata A, Amano J (2005) Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapy of tumours. Immunol Cell Biol 83:429–439PubMedCrossRefGoogle Scholar
  71. Kudo T, Nakagawa H, Takahashi M et al (2007) N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma. Mol Cancer 6:32PubMedCrossRefGoogle Scholar
  72. Kuno A, Uchiyama N, Koseki-Kuno S et al (2005) Evanescent-field fluorescence-assisted lectin microarray: a new strategy for glycan profiling. Nat Methods 2:851–856PubMedCrossRefGoogle Scholar
  73. Lagana A, Goetz JG, Cheung P et al (2006) Galectin binding to Mgat5-modified N-glycans regulates fibronectin matrix remodeling in tumor cells. Mol Cell Biol 26:3181–3193PubMedCrossRefGoogle Scholar
  74. Lau KS, Dennis JW (2008) N-Glycans in cancer progression. Glycobiology 18:750–760PubMedCrossRefGoogle Scholar
  75. Lau KS, Partridge EA, Grigorian A et al (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129:123–134PubMedCrossRefGoogle Scholar
  76. Le Pendu J, Marionneau S, Cailleau-Thomas A et al (2001) ABH and Lewis histo-blood group antigens in cancer. APMIS 109:9–31PubMedCrossRefGoogle Scholar
  77. Lee JS, Ro JY, Sahin AA et al (1991) Expression of blood-group antigen A – a favorable prognostic factor in non-small-cell lung cancer. N Engl J Med 324:1084–1090PubMedCrossRefGoogle Scholar
  78. Liang PH, Wu CY, Greenberg WA et al (2008) Glycan arrays: biological and medical applications. Curr Opin Chem Biol 12:86–92PubMedCrossRefGoogle Scholar
  79. Lloyd KO, Burchell J, Kudryashov V et al (1996) Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines. Demonstration of simpler and fewer glycan chains in tumor cells. J Biol Chem 271:33325–33334PubMedCrossRefGoogle Scholar
  80. Lowe JB (2002) Glycosylation in the control of selectin counter-receptor structure and function. Immunol Rev 186:19–36PubMedCrossRefGoogle Scholar
  81. Maemura K, Fukuda M (1992) Poly-N-acetyllactosaminyl O-glycans attached to leukosialin. The presence of sialyl Le(x) structures in O-glycans. J Biol Chem 267:24379–24386PubMedGoogle Scholar
  82. Magnani JL, Nilsson B, Brockhaus M et al (1982) A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem 257:14365–14369PubMedGoogle Scholar
  83. Magnani JL, Steplewski Z, Koprowski H et al (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res 43:5489–5492PubMedGoogle Scholar
  84. Martensson S, Bigler SA, Brown M et al (1995) Sialyl-Lewis(x) and related carbohydrate antigens in the prostate. Hum Pathol 26:735–739PubMedCrossRefGoogle Scholar
  85. McEver RP (1997) Selectin-carbohydrate interactions during inflammation and metastasis. Glycoconj J 14:585–591PubMedCrossRefGoogle Scholar
  86. Mendelsohn R, Cheung P, Berger L et al (2007) Complex N-glycan and metabolic control in tumor cells. Cancer Res 67:9771–9780PubMedCrossRefGoogle Scholar
  87. Mita Y, Aoyagi Y, Suda T et al (2000) Plasma fucosyltransferase activity in patients with hepatocellular carcinoma, with special reference to correlation with fucosylated species of alpha-fetoprotein. J Hepatol 32:946–954PubMedCrossRefGoogle Scholar
  88. Miyake M, Taki T, Hitomi S et al (1992) Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung. N Engl J Med 327:14–18PubMedCrossRefGoogle Scholar
  89. Miyoshi E, Nakano M (2008) Fucosylated haptoglobin is a novel marker for pancreatic cancer: detailed analyses of oligosaccharide structures. Proteomics 8:3257–3262PubMedCrossRefGoogle Scholar
  90. Molinari M (2007) N-glycan structure dictates extension of protein folding or onset of disposal. Nat Chem Biol 3:313–320PubMedCrossRefGoogle Scholar
  91. Moniaux N, Andrianifahanana M, Brand RE et al (2004) Multiple roles of mucins in pancreatic cancer, a lethal and challenging malignancy. Br J Cancer 91:1633–1638PubMedGoogle Scholar
  92. Naitoh A, Aoyagi Y, Asakura H (1999) Highly enhanced fucosylation of serum glycoproteins in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 14:436–445PubMedCrossRefGoogle Scholar
  93. Nguyen JT, Evans DP, Galvan M et al (2001) CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans. J Immunol 167:5697–5707PubMedGoogle Scholar
  94. Nuck R, Paul C, Wieland B et al (1993) Comparative study of high-mannose-type oligosaccharides in membrane glycoproteins of rat hepatocytes and different rat hepatoma cell lines. Eur J Biochem 216:215–221PubMedCrossRefGoogle Scholar
  95. Ohm JE, Carbone DP (2002) Immune dysfunction in cancer patients. Oncology (Huntingt) 16:11–18Google Scholar
  96. Ohyama C (2008) Glycosylation in bladder cancer. Int J Clin Oncol 13:308–313PubMedCrossRefGoogle Scholar
  97. Ohyama C, Tsuboi S, Fukuda M (1999) Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells. EMBO J 18:1516–1525PubMedCrossRefGoogle Scholar
  98. Okuyama N, Ide Y, Nakano M et al (2005) Fucosylated haptoglobin is a novel marker for pancreatic cancer: A detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation. Int J Cancer 118:2803–2808CrossRefGoogle Scholar
  99. Orchekowski R, Hamelinck D, Li L et al (2005) Antibody microarray profiling reveals individual and combined serum proteins associated with pancreatic cancer. Cancer Res 65:11193–11202PubMedCrossRefGoogle Scholar
  100. Orntoft TF, Meldgaard P, Pedersen B et al (1996) The blood group ABO gene transcript is down-regulated in human bladder tumors and growth-stimulated urothelial cell lines. Cancer Res 56:1031–1036PubMedGoogle Scholar
  101. Osako M, Yonezawa S, Siddiki B et al (1993) Immunohistochemical study of mucin carbohydrates and core proteins in human pancreatic tumors. Cancer 71:2191–2199PubMedCrossRefGoogle Scholar
  102. Partridge EA, Le Roy C, Di Guglielmo GM et al (2004) Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306:120–124PubMedCrossRefGoogle Scholar
  103. Pearlstein E, Salk PL, Yogeeswaran G et al (1980) Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line. Proc Natl Acad Sci USA 77:4336–4339PubMedCrossRefGoogle Scholar
  104. Peracaula R, Tabares G, Royle L et al (2003) Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins. Glycobiology 13:457–470PubMedCrossRefGoogle Scholar
  105. Pilobello KT, Krishnamoorthy L, Slawek D et al (2005) Development of a lectin microarray for the rapid analysis of protein glycopatterns. Chembiochem 6:985–989PubMedCrossRefGoogle Scholar
  106. Radhakrishnan P, Lin MF, Cheng PW (2008) Elevated expression of L-selectin ligand in lymph node-derived human prostate cancer cells correlates with increased tumorigenicity. Glycoconj J 26:75–81PubMedCrossRefGoogle Scholar
  107. Ragupathi G, Gathuru J, Livingston P (2005) Antibody inducing polyvalent cancer vaccines. Cancer Treat Res 123:157–180PubMedCrossRefGoogle Scholar
  108. Raman R, Raguram S, Venkataraman G et al (2005) Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods 2:817–824PubMedCrossRefGoogle Scholar
  109. Ryder SD, Smith JA, Rhodes JM (1992) Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells. J Natl Cancer Inst 84:1410–1416PubMedCrossRefGoogle Scholar
  110. Saeland E, van Vliet SJ, Backstrom M et al (2007) The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma. Cancer Immunol Immunother 56:1225–1236PubMedCrossRefGoogle Scholar
  111. Saito H, Nishikawa A, Gu J et al (1994) cDNA cloning and chromosomal mapping of human N-acetylglucosaminyltransferase V+. Biochem Biophys Res Commun 198:318–327PubMedCrossRefGoogle Scholar
  112. Samak R, Edelstein R, Israel L (1982) Immunosuppressive effect of acute-phase reactant proteins in vitro and its relevance to cancer. Cancer Immunol Immunother 13:38–43PubMedCrossRefGoogle Scholar
  113. Satomura Y, Sawabu N, Takemori Y et al (1991) Expression of various sialylated carbohydrate antigens in malignant and nonmalignant pancreatic tissues. Pancreas 6:448–458PubMedCrossRefGoogle Scholar
  114. Saul R, Molyneux RJ and Elbein AD (1984) Studies on the mechanism of castanospermine inhibition of alpha- and beta-glucosidases. Arch Biochem Biophys 230:668–675PubMedCrossRefGoogle Scholar
  115. Schachter H and Brockhausen I (1989) The biosynthesis of branched O-glycans. Symp Soc Exp Biol 43:1–26PubMedGoogle Scholar
  116. Schena M, Shalon D, Davis RW et al (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470PubMedCrossRefGoogle Scholar
  117. Schuessler MH, Pintado S, Welt S et al (1991) Blood group and blood-group-related antigens in normal pancreas and pancreas cancer: enhanced expression of precursor type 1, Tn and sialyl-Tn in pancreas cancer. Int J Cancer 47:180–187PubMedCrossRefGoogle Scholar
  118. Sewell R, Backstrom M, Dalziel M et al (2006) The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer. J Biol Chem 281:3586–3594PubMedCrossRefGoogle Scholar
  119. Shimizu K, Katoh H, Yamashita F et al (1996) Comparison of carbohydrate structures of serum alpha-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis. Clin Chim Acta 254:23–40PubMedCrossRefGoogle Scholar
  120. Shimodaira K, Nakayama J, Nakamura N et al (1997) Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression. Cancer Res 57:5201–5206PubMedGoogle Scholar
  121. Siddiqui SF, Pawelek J, Handerson T et al (2005) Coexpression of beta1,6-N-acetylglucosaminyltransferase V glycoprotein substrates defines aggressive breast cancers with poor outcome. Cancer Epidemiol Biomarkers Prev 14:2517–2523PubMedCrossRefGoogle Scholar
  122. Singh M, Maitra A (2007) Precursor lesions of pancreatic cancer: molecular pathology and clinical implications. Pancreatology 7:9–19PubMedCrossRefGoogle Scholar
  123. Singh R, Subramanian S, Rhodes JM et al (2006) Peanut lectin stimulates proliferation of colon cancer cells by interaction with glycosylated CD44v6 isoforms and consequential activation of c-Met and MAPK: functional implications for disease-associated glycosylation changes. Glycobiology 16:594–601PubMedCrossRefGoogle Scholar
  124. Springer GF (1984) T and Tn, general carcinoma autoantigens. Science 224:1198–1206PubMedCrossRefGoogle Scholar
  125. Springer GF (1997) Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J Mol Med 75:594–602PubMedCrossRefGoogle Scholar
  126. Takahashi S, Oda T, Hasebe T et al (2001) Overexpression of sialyl Lewis x antigen is associated with formation of extratumoral venous invasion and predicts postoperative development of massive hepatic metastasis in cases with pancreatic ductal adenocarcinoma. Pathobiology 69:127–135PubMedCrossRefGoogle Scholar
  127. Tang DG, Honn KV (1994) Adhesion molecules and tumor metastasis: an update. Invasion Metastasis 14:109–122PubMedGoogle Scholar
  128. Tarp MA, Clausen H (2008) Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim Biophys Acta 1780:546–563PubMedGoogle Scholar
  129. Taylor ME, Drickamer K (2007) Paradigms for glycan-binding receptors in cell adhesion. Curr Opin Cell Biol 19:572–577PubMedCrossRefGoogle Scholar
  130. Thompson S, Cantwell BM, Cornell C et al (1991) Abnormally-fucosylated haptoglobin: a cancer marker for tumour burden but not gross liver metastasis. Br J Cancer 64:386–390PubMedGoogle Scholar
  131. Thompson S, Guthrie D, Turner GA (1988) Fucosylated forms of alpha-1-antitrypsin that predict unresponsiveness to chemotherapy in ovarian cancer. Br J Cancer 58:589–593PubMedGoogle Scholar
  132. Thompson S, Stappenbeck R, Turner GA (1989) A multiwell lectin-binding assay using lotus tetragonolobus for measuring different glycosylated forms of haptoglobin. Clin Chim Acta 180:277–284PubMedCrossRefGoogle Scholar
  133. Valenzuela HF, Pace KE, Cabrera PV et al (2007) O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1. Cancer Res 67:6155–6162PubMedCrossRefGoogle Scholar
  134. van Dijk W, Havenaar EC, Brinkman-van der Linden EC (1995) Alpha 1-acid glycoprotein (orosomucoid): pathophysiological changes in glycosylation in relation to its function. Glycoconj J 12:227–233PubMedCrossRefGoogle Scholar
  135. van Vliet SJ, van Liempt E, Geijtenbeek TB et al (2006) Differential regulation of C-type lectin expression on tolerogenic dendritic cell subsets. Immunobiology 211:577–585PubMedCrossRefGoogle Scholar
  136. Varki A, Cummings R, Esko J et al (1999). Essentials of glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYGoogle Scholar
  137. Wolf MF, Ludwig A, Fritz P et al (1988) Increased expression of Thomsen−Friedenreich antigens during tumor progression in breast cancer patients. Tumour Biol 9:190–194PubMedCrossRefGoogle Scholar
  138. Wong K, Easton R, Panico M et al (2003) Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125. J Biol Chem 278:28619–28634CrossRefGoogle Scholar
  139. Xia L, Ju T, Westmuckett A et al (2004) Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1-derived O-glycans. J Cell Biol 164:451–459PubMedCrossRefGoogle Scholar
  140. Yeo CJ, Cameron JL, Lillemoe KD et al (1995) Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221:721–731; discussion 731–723Google Scholar
  141. Yogeeswaran G, Salk PL (1981) Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines. Science 212:1514–1516PubMedCrossRefGoogle Scholar
  142. Yu LG (2007) The oncofetal Thomsen−Friedenreich carbohydrate antigen in cancer progression. Glycoconj J 24:411–420PubMedCrossRefGoogle Scholar
  143. Yu LG, Andrews N, Zhao Q et al (2007) Galectin-3 interaction with Thomsen−Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion. J Biol Chem 282:773–781PubMedCrossRefGoogle Scholar
  144. Zhang K, Baeckstrom D, Brevinge H et al (1996) Secreted MUC1 mucins lacking their cytoplasmic part and carrying sialyl-Lewis a and x epitopes from a tumor cell line and sera of colon carcinoma patients can inhibit HL-60 leukocyte adhesion to E-selectin-expressing endothelial cells. J Cell Biochem 60:538–549PubMedCrossRefGoogle Scholar
  145. Zhang K, Sikut R, Hansson GC (1997) A MUC1 mucin secreted from a colon carcinoma cell line inhibits target cell lysis by natural killer cells. Cell Immunol 176:158–165PubMedCrossRefGoogle Scholar
  146. Zhang J, Nakayama J, Ohyama C et al (2002) Sialyl Lewis X-dependent lung colonization of B16 melanoma cells through a selectin-like endothelial receptor distinct from E- or P-selectin. Cancer Res 62:4194–4198PubMedGoogle Scholar
  147. Zhao J, Patwa TH, Qiu W et al (2007) Glycoprotein microarrays with multi-lectin detection: unique lectin binding patterns as a tool for classifying normal, chronic pancreatitis and pancreatic cancer sera. J Proteome Res 6:1864–1874PubMedCrossRefGoogle Scholar
  148. Zhao YY, Takahashi M, Gu JG et al (2008) Functional roles of N-glycans in cell signaling and cell adhesion in cancer. Cancer Sci 99:1304–1310PubMedCrossRefGoogle Scholar
  149. Zheng T, Peelen D and Smith LM (2005) Lectin arrays for profiling cell surface carbohydrate expression. J Am Chem Soc 127:9982–9983PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Van Andel Research InstituteGrand RapidsUSA

Personalised recommendations