Introduction to glycopathology: the concept, the tools and the perspectives

Diagnostic Pathology

Klaus Kayser²  Hans-Joachim Gabius¹ 

[1] Chair of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr 13, D-80539, Munich, Germany;UICC-TPCC, Institut für Pathologie, Charite, Charite Platz 1, 10118, Berlin, Germany

关键词: Neoglycoconjugates;    Lectin;    Glycosylation;    Glycobiology;    Agglutinin;   

Others  :  803588
DOI  :  10.1186/1746-1596-9-4

 received in 2013-12-05, accepted in 2013-12-06,  发布年份 2014

【 摘 要 】

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1670639891114983 webcite.

Analyzing the flow of biological information is a fundamental challenge for basic sciences. The emerging results will then lend themselves to the development of new approaches for medical applications. Toward this end, the products of protein/lipid glycosylation deserve special attention. The covalent attachment of sugars to these carriers means much more than just a change of the carriers’ physicochemical properties. In principle, the ubiquitous presence of glycoconjugates and the close inspection of the particular structural ‘talents’ of carbohydrates provide suggestive evidence for information coding by sugars. In fact, the theoretical number of ‘words’ (oligomers) formed by ‘letters’ (monosaccharides) is by far higher than by using nucleotides or amino acids. In other words, glycans harbor an unsurpassed coding capacity. The cyto- and histochemical detection of dynamic changes in the profile of cellular glycans (glycome, the equivalent of the proteome) by sugar receptors such as antibodies used as tools underscores the suitability of carbohydrates for such a task. The resulting staining patterns can be likened to a molecular fingerprint. By acting as ligand (counterreceptor) for endogenous receptors (tissue lectins), glycan epitopes become partners in a specific recognition pair, and the sugar-encoded information can then be translated into effects, e.g. in growth regulation. Of note, expression of both sides of such a pair, i.e. lectin and cognate glycan, can physiologically be orchestrated for optimal efficiency. Indeed, examples how to prevent autoimmune diseases by regulatory T cells and restrict carcinoma growth by a tumor suppressor attest occurrence of co-regulation. In consequence, these glycans have potential to establish a new class of functional biomarkers, and mapping presence of their receptors is warranted. In this review, the cyto- and histochemical methods, which contribute to explore information storage and transfer within the sugar code, are described. This introduction to the toolbox is flanked by illustrating the application of each type of tool in histopathology, with focus on adhesion/growth-regulating galectins. Together with an introduction to fundamental principles of the sugar code, the review is designed to guide into this field and to inspire respective research efforts.

【 授权许可】

   
2014 Gabius and Kayser; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Rüdiger H, Gabius H-J: The biochemical basis and coding capacity of the sugar code. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:3-13.
• [2]Laine RA: The information-storing potential of the sugar code. In Glycosciences: Status and Perspectives. Edited by Gabius H-J, Gabius S. London - Weinheim: Chapman & Hall; 1997:1-14.
• [3]Merzendorfer H: Chitin: structure, function and metabolism. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:217-229.
• [4]Reuter G, Gabius H-J: Eukaryotic glycosylation: whim of nature or multipurpose tool? Cell Mol Life Sci 1999, 55(3):368-422.
• [5]Buddecke E: Proteoglycans. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:199-216.
• [6]Kopitz J: Glycolipids. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:177-198.
• [7]Patsos G, Corfield A: O-Glycosylation: structural diversity and function. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:111-137.
• [8]Zuber C, Roth J: N-Glycosylation. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:87-110.
• [9]Spiro RG: Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 2002, 12(4):43R-56R.
• [10]Gabius HJ, André S, Kaltner H, Siebert HC: The sugar code: functional lectinomics. Biochim Biophys Acta 2002, 1572(2–3):165-177.
• [11]Roseman S: Reflections on glycobiology. J Biol Chem 2001, 276(45):41527-41542.
• [12]Nakagawa H: Analytical aspects: analysis of protein-bound glycans. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:71-83.
• [13]Mechref Y, Hu Y, Garcia A, Hussein A: Identifying cancer biomarkers by mass spectrometry-based glycomics. Electrophoresis 2012, 33(12):1755-1767.
• [14]Galli C, Basso D, Plebani M: CA 19-9: handle with care. Clin Chem Lab Med 2013, 51(7):1369-1383.
• [15]Novotny MV, Alley WR Jr, Mann BF: Analytical glycobiology at high sensitivity: current approaches and directions. Glycoconj J 2013, 30(2):89-117.
• [16]Schrével J, Gros D, Monsigny M: Cytochemistry of cell glycoconjugates. Progr Histochem Cytochem 1981, 14(2):1-269.
• [17]Caselitz J: Lectins and blood group substances as “tumor markers”. Curr Top Pathol 1987, 77:245-277.
• [18]Damjanov I: Lectin cytochemistry and histochemistry. Lab Invest 1987, 57(1):5-20.
• [19]Spicer SS, Schulte BA: Diversity of cell glycoconjugates shown histochemically: a perspective. J Histochem Cytochem 1992, 40:1-38.
• [20]Danguy A, Akif F, Pajak B, Gabius H-J: Contribution of carbohydrate histochemistry to glycobiology. Histol Histopathol 1994, 9:155-171.
• [21]Roth J: Lectins for histochemical demonstration of glycans. Histochem Cell Biol 2011, 136(2):117-130.
• [22]Schwarz HP, Dorner F: Karl Landsteiner and his major contributions to haematology. Br J Haematol 2003, 121(4):556-565.
• [23]Boyd WC: The lectins: their present status. Vox Sang 1963, 8:1-32.
• [24]Watkins WM: A half century of blood-group antigen research: some personal recollections. Trends Glycosci Glycotechnol 1999, 11:391-411.
• [25]Rüdiger H, Gabius H-J: The history of lectinology. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:261-268.
• [26]Patsos G, André S, Roeckel N, Gromes R, Gebert J, Kopitz J, Gabius H-J: Compensation of loss of protein function in microsatellite-unstable colon cancer cells (HCT116): a gene-dependent effect on the cell surface glycan profile. Glycobiology 2009, 19(7):726-734.
• [27]van de Wouwer M, André S, Gabius H-J, Villalobo A: Nitric oxide changes distinct aspects of the glycophenotype of human neuroblastoma NB69 cells. Nitric Oxide 2011, 24(2):91-101.
• [28]Gebert J, Kloor M, Lee J, Lohr M, André S, Wagner R, Kopitz J, Gabius H-J: Colonic carcinogenesis along different genetic routes: glycophenotyping of tumor cases separated by microsatellite instability/stability. Histochem Cell Biol 2012, 138(2):339-350.
• [29]Unverzagt C, André S, Seifert J, Kojima S, Fink C, Srikrishna G, Freeze H, Kayser K, Gabius H-J: Structure-activity profiles of complex biantennary glycans with core fucosylation and with/without additional α2,3/α2,6-sialylation: synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake. J Med Chem 2002, 45(2):478-491.
• [30]André S, Unverzagt C, Kojima S, Frank M, Seifert J, Fink C, Kayser K, von der Lieth C-W, Gabius H-J: Determination of modulation of ligand properties of synthetic complex-type biantennary N-glycans by introduction of bisecting GlcNAc in silico, in vitro and in vivo. Eur J Biochem 2004, 271(1):118-134.
• [31]André S, Kozár T, Schuberth R, Unverzagt C, Kojima S, Gabius H-J: Substitutions in the N-glycan core as regulators of biorecognition: the case of core-fucose and bisecting GlcNAc moieties. Biochemistry 2007, 46:6984-6995.
• [32]André S, Kozár T, Kojima S, Unverzagt C, Gabius H-J: From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans. Biol Chem 2009, 390(7):557-565.
• [33]Takahashi M, Kuroki Y, Ohtsubo K, Taniguchi N: Core fucose and bisecting GlcNAc, the direct modifiers of the N-glycan core: their functions and target proteins. Carbohydr Res 2009, 344(12):1387-1390.
• [34]Gabius H-J, van de Wouwer M, André S, Villalobo A: Down-regulation of the epidermal growth factor receptor by altering N-glycosylation: emerging role of β1,4-galactosyltransferases. Anticancer Res 2012, 32(5):1565-1572.
• [35]Cooper DNW: Galectinomics: finding themes in complexity. Biochim Biophys Acta 2002, 1572:209-231.
• [36]Gready JN, Zelensky AN: Routes in lectin evolution: case study on the C-type lectin-like domains. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:329-346.
• [37]Pál Z, Antal P, Srivastava SK, Hullám G, Semsei AF, Gál J, Svébis M, Soós G, Szalai C, André S, et al.: Non-synonymous single nucleotide polymorphisms in genes for immunoregulatory galectins: association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population. Biochim Biophys Acta 2012, 1820(10):1512-1518.
• [38]Kaltner H, Gabius H-J: A toolbox of lectins for translating the sugar code: the galectin network in phylogenesis and tumors. Histol Histopathol 2012, 27(4):397-416.
• [39]Kaltner H, Raschta A-S, Manning JC, Gabius H-J: Copy-number variation of functional galectin genes: Studying animal galectin-7 (p53-induced gene 1 in man) and tandem-repeat-type galectins-4 and -9. Glycobiology 2013, 23(10):1152-1163.
• [40]von der Lieth C-W, Siebert H-C, Kozár T, Burchert M, Frank M, Gilleron M, Kaltner H, Kayser G, Tajkhorshid E, Bovin NV, et al.: Lectin ligands: new insights into their conformations and their dynamic behavior and the discovery of conformer selection by lectins. Acta Anat 1998, 161(1–4):91-109.
• [41]Gabius H-J, André S, Jiménez-Barbero J, Romero A, Solís D: From lectin structure to functional glycomics: principles of the sugar code. Trends Biochem Sci 2011, 36(6):298-313.
• [42]Gabius H-J: Animal and human lectins. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:317-328.
• [43]Gabius H-J, Springer WR, Barondes SH: Receptor for the cell binding site of discoidin I. Cell 1985, 42:449-456.
• [44]Takahashi K, Ip WE, Michelow IC, Ezekowitz RA: The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol 2006, 18(1):16-23.
• [45]Thiel S: Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol 2007, 44(16):3875-3888.
• [46]Delacour D, Gouyer V, Zanetta J-P, Drobecq H, Leteurtre E, Grard G, Moreau-Hannedouche O, Maes E, Pons A, André S, et al.: Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells. J Cell Biol 2005, 169(3):491-501.
• [47]Stechly L, Morelle W, Dessein AF, André S, Grard G, Trinel D, Dejonghe MJ, Leteurtre E, Drobecq H, Trugnan G, et al.: Galectin-4-regulated delivery of glycoproteins to the brush border membrane of enterocyte-like cells. Traffic 2009, 10(4):438-450.
• [48]Kollmann K, Pohl S, Marschner K, Encarnacao M, Sakwa I, Tiede S, Poorthuis BJ, Lubke T, Muller-Loennies S, Storch S, et al.: Mannose phosphorylation in health and disease. Eur J Cell Biol 2010, 89(1):117-123.
• [49]Velasco S, Díez-Revuelta N, Hernández-Iglesias T, Kaltner H, André S, Gabius H-J, Abad-Rodriguez J: Neuronal galectin-4 is required for axon growth and for the organization of axonal membrane L1 delivery and clustering. J Neurochem 2013, 125(1):49-62.
• [50]Reuter G, Gabius H-J: Sialic acids. Structure, analysis, metabolism, and recognition. Biol Chem Hoppe-Seyler 1996, 377:325-342.
• [51]André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, et al.: Tumor suppressor p16INK4a: modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells. FEBS J 2007, 274:3233-3256.
• [52]Sanchez-Ruderisch H, Fischer C, Detjen KM, Welzel M, Wimmel A, Manning JC, André S, Gabius H-J: Tumor suppressor p16INK4a: downregulation of galectin-3, an endogenous competitor of the pro-anoikis effector galectin-1, in a pancreatic carcinoma model. FEBS J 2010, 277(17):3552-3563.
• [53]Amano M, Eriksson H, Manning JC, Detjen KM, André S, Nishimura S-I, Lehtiö J, Gabius H-J: Tumour suppressor p16INK4a: anoikis-favouring decrease in N/O-glycan/cell surface sialylation by down-regulation of enzymes in sialic acid biosynthesis in tandem in a pancreatic carcinoma model. FEBS J 2012, 279(21):4062-4080.
• [54]Kopitz J, von Reitzenstein C, Burchert M, Cantz M, Gabius H-J: Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. J Biol Chem 1998, 273(18):11205-11211.
• [55]Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius H-J: Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem 2001, 276(38):35917-35923.
• [56]Wang J, Lu ZH, Gabius H-J, Rohowsky-Kochan C, Ledeen RW, Wu G: Cross-linking of GM1 ganglioside by galectin-1 mediates regulatory T cell activity involving TRPC5 channel activation: possible role in suppressing experimental autoimmune encephalomyelitis. J Immunol 2009, 182(7):4036-4045.
• [57]Kopitz J, Bergmann M, Gabius H-J: How adhesion/growth-regulatory galectins-1 and -3 attain cell specificity: case study defining their target on neuroblastoma cells (SK-N-MC) and marked affinity regulation by affecting microdomain organization of the membrane. IUBMB Life 2010, 62(8):624-628.
• [58]Wu G, Lu ZH, Gabius H-J, Ledeen RW, Bleich D: Ganglioside GM1 deficiency in effector T cells from NOD mice induces resistance to regulatory T cell suppression. Diabetes 2011, 60(9):2341-2349.
• [59]Gabius H-J, Engelhardt R, Rehm S, Cramer F: Biochemical characterization of endogenous carbohydrate-binding proteins from spontaneous murine rhabdomyosarcoma, mammary adenocarcinoma, and ovarian teratoma. J Natl Cancer Inst 1984, 73:1349-1357.
• [60]Gabius H-J, Engelhardt R, Cramer F, Bätge R, Nagel GA: Pattern of endogenous lectins in a human epithelial tumor. Cancer Res 1985, 45:253-257.
• [61]Gabius H-J: Glycobiomarkers by glycoproteomics and glycan profiling (glycomics): emergence of functionality. Biochem Soc Trans 2011, 39(1):399-405.
• [62]Smetana K Jr, André S, Kaltner H, Kopitz J, Gabius H-J: Context-dependent multifunctionality of galectin-1: a challenge for defining the lectin as therapeutic target. Expert Opin Ther Targets 2013, 17(4):379-392.
• [63]Oscarson S: The chemist’s way to synthesize glycosides. In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:31-51.
• [64]Stowell CP, Lee YC: Neoglycoproteins: the preparation and application of synthetic glycoproteins. Adv Carbohydr Chem Biochem 1980, 37:225-281.
• [65]Aplin JD, Wriston JC Jr: Preparation, properties and applications of carbohydrate conjugates of proteins and lipids. CRC Crit Rev Biochem 1981, 10:259-306.
• [66]Gabius H-J, Gabius S, Zemlyanukhina TV, Bovin NV, Brinck U, Danguy A, Joshi SS, Kayser K, Schottelius J, Sinowatz F, et al.: Reverse lectin histochemistry: design and application of glycoligands for detection of cell and tissue lectins. Histol Histopathol 1993, 8(2):369-383.
• [67]Lee YC, Lee RT (Eds): Neoglycoconjugates. Preparation and Applications. San Diego: Academic; 1994.
• [68]Hardonk MJ, Scholtens HB: A histochemical study about the zonal distribution of the galactose-binding protein in rat liver. Histochemistry 1980, 69:289-297.
• [69]Straus W: Cytochemical detection of mannose-specific receptors for glycoproteins with horseradish peroxidase as a ligand. Histochemistry 1981, 73:39-47.
• [70]Straus W, Keller JM: Unusual binding sites for horseradish peroxidase on the surface of cultured and isolated mammalian cells. Suppression of binding by certain nucleotides and glycoproteins, and a role for calcium. Histochemistry 1986, 85(4):277-285.
• [71]Gabius H-J, Engelhardt R, Hellmann K-P, Hellmann T, Ochsenfahrt A: Preparation of neoglycoprotein-enzyme conjugate using a heterobifunctional reagent and its use in solid-phase assay and histochemistry. Anal Biochem 1987, 165:349-355.
• [72]Gabius S, Hellmann KP, Hellmann T, Brinck U, Gabius H-J: Neoglycoenzymes: a versatile tool for lectin detection in solid-phase assays and glycohistochemistry. Anal Biochem 1989, 182:447-451.
• [73]André S, Kopitz J, Kaltner H, Villalobo A, Gabius H-J: Glycans as functional markers in malignancy? In The Sugar Code. Fundamentals of glycosciences. Edited by Gabius H-J. Weinheim, Germany: Wiley-VCH; 2009:419-432.
• [74]Bardosi A, Dimitri T, Gabius H-J: (Neo)glycoproteins as tools in neuropathology: histochemical patterns of the extent of expression of endogenous carbohydrate-binding receptors, like lectins, in meningiomas. Virchows Arch [Cell Pathol] 1988, 56:35-43.
• [75]Gabius H-J, Bodanowitz S, Schauer A: Endogenous sugar-binding proteins in human breast tissue and benign and malignant breast lesions. Cancer 1988, 61:1125-1131.
• [76]Kayser K, Gabius HJ, Ciesiolka T, Ebert W, Bach S: Histopathologic evaluation of application of labeled neoglycoproteins in primary bronchus carcinoma. Hum Pathol 1989, 20(4):352-360.
• [77]Danguy A, Kayser K, Bovin NV, Gabius H-J: The relevance of neoglycoconjugates for histology and pathology. Trends Glycosci Glycotechnol 1995, 7:261-275.
• [78]Kayser K, Böhm G, Blum S, Beyer M, Zink S, André S, Gabius H-J: Glyco- and immunohistochemical refinement of the differential diagnosis between mesothelioma and metastatic carcinoma and survival analysis of patients. J Pathol 2001, 193:175-180.
• [79]Kayser K, Kayser C, Rahn W, Bovin NV, Gabius H-J: Carcinoid tumors of the lung: immuno- and ligandohistochemistry, analysis of integrated optical density, syntactic structure analysis, clinical data, and prognosis of patients treated surgically. J Surg Oncol 1996, 63:99-106.
• [80]Gabius H-J, Schröter C, Gabius S, Brinck U, Tietze L-F: Binding of T-antigen-bearing neoglycoprotein and peanut agglutinin to cultured tumor cells and breast carcinomas. J Histochem Cytochem 1990, 38:1625-1631.
• [81]Kayser K, Bovin NV, Korchagina EY, Zeilinger C, Zeng F-Y, Gabius H-J: Correlation of expression of binding sites for synthetic blood group A-, B-, and H-trisaccharides and for sarcolectin with survival of patients with bronchial carcinoma. Eur J Cancer 1994, 30A(5):653-657.
• [82]Wu AM, Wu JH, Liu J-H, Singh T, André S, Kaltner H, Gabius H-J: Effects of polyvalency of glycotopes and natural modifications of human blood group ABH/Lewis sugars at the Galβ1-terminated core saccharides on the binding of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N). Biochimie 2004, 86:317-326.
• [83]Krzeminski M, Singh T, André S, Lensch M, Wu AM, Bonvin AMJJ, Gabius H-J: Human galectin-3 (Mac-2 antigen): defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region. Biochim Biophys Acta 2011, 1810(2):150-161.
• [84]Bardosi A, Dimitri T, Wosgien B, Gabius H-J: Expression of endogenous receptors for neoglycoproteins, especially lectins, which allow fiber typing on formaldehyde-fixed, paraffin-embedded muscle biopsy specimens. A glycohistochemical, immunohistochemical and glycobiochemical study. J Histochem Cytochem 1989, 37:989-998.
• [85]Gabius H-J, Brehler R, Schauer A, Cramer F: Localization of endogenous lectins in normal human breast, benign breast lesions and mammary carcinomas. Virch Arch [Cell Pathol] 1986, 52(2):107-115.
• [86]Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector J-C, et al.: Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor. Gut 2002, 50(3):392-401.
• [87]Nagy N, Legendre H, Engels O, André S, Kaltner H, Wasano K, Zick Y, Pector J-C, Decaestecker C, Gabius H-J, et al.: Refined prognostic evaluation in colon cancer using immunohistochemical galectin fingerprinting. Cancer 2003, 97:1849-1858.
• [88]Saussez S, Cucu D-R, Decaestecker C, Chevalier D, Kaltner H, André S, Wacreniez A, Toubeau G, Camby I, Gabius H-J, et al.: Galectin-7 (p53-induced gene-1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Ann Surg Oncol 2006, 13:999-1009.
• [89]Cludts S, Decaestecker C, Mahillon V, Chevalier D, Kaltner H, André S, Remmelink M, Leroy X, Gabius H-J, Saussez S: Galectin-8 up-regulation during hypopharyngeal and laryngeal tumor progression and comparison with galectins-1, -3 and -7. Anticancer Res 2009, 29(12):4933-4940.
• [90]Langbein S, Brade J, Badawi JK, Hatzinger M, Kaltner H, Lensch M, Specht K, André S, Brinck U, Alken P, et al.: Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance. Histopathology 2007, 51(5):681-690.
• [91]Saussez S, de Leval L, Decaestecker C, Sirtaine N, Cludts S, Duray A, Chevalier D, André S, Gabius H-J, Remmelink M, et al.: Galectin fingerprinting in Warthin’s tumors: lectin-based approach to trace its origin? Histol Histopathol 2010, 25(5):541-550.
• [92]Remmelink M, de Leval L, Decaestecker C, Duray A, Crompot E, Sirtaine N, André S, Kaltner H, Leroy X, Gabius H-J, et al.: Quantitative immunohistochemical fingerprinting of adhesion/growth-regulatory galectins in salivary gland tumours: divergent profiles with diagnostic potential. Histopathology 2011, 58(4):543-556.
• [93]Kayser K, Gabius H-J: Graph theory and the entropy concept in histochemistry. Theoretical considerations, application in histopathology and the combination with receptor-specific approaches. Progr Histochem Cytochem 1997, 32(2):1-106.
• [94]Kayser K, Gabius H-J: The application of thermodynamic principles to histochemical and morphometric tissue research: principles and practical outline with focus on glycosciences. Cell Tissue Res 1999, 296:443-455.
• [95]Kayser K, Höft D, Hufnagl P, Caselitz J, Zick Y, André S, Kaltner H, Gabius H-J: Combined analysis of tumor growth pattern and expression of endogenous lectins as a prognostic tool in primary testicular cancer and its lung metastases. Histol Histopathol 2003, 18:771-779.
• [96]Gabius H-J, Wosgien B, Brinck U, Schauer A: Localization of endogenous β-galactoside-specific lectins by neoglycoproteins, lectin-binding tissue glycoproteins and antibodies and of accessible lectin-specific ligands by a mammalian lectin in human breast cancer. Pathol Res Pract 1991, 187(7):839-847.
• [97]Purkrábková T, Smetana K Jr, Dvoránková B, Holíková Z, Böck C, Lensch M, André S, Pytlík R, Liu F-T, Klíma J, et al.: New aspects of galectin functionality in nuclei of cultured bone marrow stromal and epidermal cells: biotinylated galectins as tool to detect specific binding sites. Biol Cell 2003, 95:535-545.
• [98]Saal I, Nagy N, Lensch M, Lohr M, Manning JC, Decaestecker C, André S, Kiss R, Salmon I, Gabius H-J: Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as histochemical tool for ligand localization. Histol Histopathol 2005, 20:1191-1208.
• [99]Habermann FA, André S, Kaltner H, Kübler D, Sinowatz F, Gabius H-J: Galectins as tools for glycan mapping in histology: comparison of their binding profiles to the bovine zona pellucida by confocal laser scanning microscopy. Histochem Cell Biol 2011, 135(6):539-552.
• [100]Kodet O, Dvoránková B, Lacina L, André S, Kaltner H, Gabius H-J, Smetana K Jr: Comparative analysis of nuclear presence of adhesion/growth-regulatory galectins and galectin reactivity in interphasic and mitotic cells. Folia Biol (Praha) 2011, 57:125-132.
• [101]Schlötzer-Schrehardt U, André S, Janko C, Kaltner H, Kopitz J, Gabius H-J, Herrmann M: Adhesion/growth-regulatory galectins in the human eye: localization profiles and tissue reactivities as a standard to detect disease-associated alterations. Graefes Arch Clin Exp Ophthalmol 2012, 250(8):1169-1180.
• [102]Plzák J, Betka J, Smetana K Jr, Chovanec M, Kaltner H, André S, Kodet R, Gabius H-J: Galectin-3: an emerging prognostic indicator in advanced head and neck carcinoma. Eur J Cancer 2004, 40(15):2324-2330.
• [103]Dawson H, André S, Karamitopoulou E, Zlobec I, Gabius H-J: The growing galectin network in colon cancer and clinical relevance of cytoplasmic galectin-3 reactivity. Anticancer Res 2013, 33(8):3053-3059.
• [104]Kopitz J, Ballikaya S, André S, Gabius H-J: Ganglioside GM1/galectin-dependent growth regulation in human neuroblastoma cells: special properties of bivalent galectin-4 and significance of linker length for ligand selection. Neurochem Res 2012, 37(6):1267-1276.
• [105]Kopitz J, Fík Z, André S, Smetana K Jr, Gabius H-J: Single-site mutational engineering and following monoPEGylation of the human lectin galectin-2: effects on ligand binding, functional aspects, and clearance from serum. Mol Pharmaceut 2013, 10(5):2054-2061.
• [106]Fischer C, Sanchez-Ruderisch H, Welzel M, Wiedenmann B, Sakai T, André S, Gabius H-J, Khachigian L, Detjen K, Rosewicz S: Galectin-1 interacts with the α5β1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p27. J Biol Chem 2005, 280:37266-37277.
• [107]Sanchez-Ruderisch H, Detjen KM, Welzel M, André S, Fischer C, Gabius H-J, Rosewicz S: Galectin-1 sensitizes carcinoma cells to anoikis via the fibronectin receptor α5β1-integrin. Cell Death Differ 2011, 18(5):806-816.
• [108]Rappl G, Abken H, Muche JM, Sterry W, Tilgen W, André S, Kaltner H, Ugurel S, Gabius H-J, Reinhold U: CD4+CD7- leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death. Leukemia 2002, 16(5):840-845.
• [109]Kayser K, Märkle C, Kugler C, André S, Schüring M-P, Zeng F-Y, Gabius H-J: Integrated nuclear fluorescence and expression of hormone-binding sites in malignant pleural effusions. Anal Quant Cytol Histol 2000, 22:364-372.
• [110]Kayser K, Gabius H-J, Köhler A, Runtsch T: Binding of neuroendocrine markders and biotinylated sex hormones and the survival n human lung cancer. Lung Cancer 1990, 6:171-183.
• [111]Kayser K, Kayser G, André S, Altiner M, Gabius H-J: Evaluation of histochemical anthracyclin binding as potential prognostic parameter in small cell lung cancer. Oncol Rep 1999, 6:1153-1157.
• [112]Kayser K, Bubenzer J, Kayser G, Eichhorn S, Zemlyanukhina TV, Bovin NV, André S, Koopmann J, Gabius H-J: Expression of lectin-, interleukin-2-, and histo-blood group-binding sites in prostate cancer and its correlation to integrated optical density and syntactic structure analysis. Analyt Quant Cytol Histol 1995, 17:135-142.
• [113]Kayser K, Nwoye JO, Kosjerina S, Goldmann T, Vollmer E, Kaltner H, André S, Gabius H-J: Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical, glycohistochemical and structural features including newly defined growth regulators and vascularization. Lung Cancer 2003, 42:171-182.
• [114]Kayser K, Gabius HJ: Analysis of expression of erythropoietin-binding sites in human lung carcinoma by the biotinylated ligand. Zentralbl Pathol 1992, 138(4):266-270.
• [115]Kayser K, Weisse G, Gabius HJ, Bubenzer J, von Eberstein M, Hintze T: Differentiation-related expression of epidermal growth factor receptors in human lung carcinoma demonstrated histochemically by biotinylated epidermal growth factor. Mod Pathol 1990, 3(3):327-331.
• [116]Kayser K, Weisse G, Gabius HJ, Hintze T: Biotinylated epidermal growth factor: a useful tool for the histochemical analysis of specific binding sites. Histochem J 1990, 22(8):426-432.
• [117]Zeng F-Y, Weiser WY, Kratzin H, Stahl B, Karas M, Gabius H-J: The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor. Arch Biochem Biophys 1993, 303:74-80.
• [118]Zeng F-Y, Gerke V, Gabius H-J: Characterization of the macrophage migration inhibitory factor-binding site of sarcolectin and its relationship to human serum albumin. Biochem Biophys Res Commun 1994, 200(1):89-94.