title: Colonic carcinogenesis along different genetic routes: glycophenotyping of tumor cases separated by microsatellite instability/stability.
abstract: Different genetic routes account for colonic carcinogenesis. However, when analyzing colon cancer specimens, separation into different groups based on genetic alterations is commonly not performed. Thus, we here initiate the comparative phenotyping considering microsatellite instability/stability for clinical specimens. The focus is given to glycan epitopes, expression of which is known to be modulated by signal-transducing proteins that act as key regulators of normal colon epithelial growth and differentiation. In addition to six plant lectins used as sensors, the presence of two adhesion/growth-regulatory galectins is studied. Overall, a considerable level of intra- and interindividual heterogeneity is revealed. Alterations in the proportion of stained cells between tumor-adjacent and malignant epithelia concerned plant lectins, which bind substituted N-glycan cores, α2,6-sialylated branch ends, core 1 O-glycans and N-acetylgalactosamine. A tendency for changes was noted between microsatellite-unstable and microsatellite-stable cases for core substitution (bisected N-glycan, presence of β1,6-branching) and status of α2,6-sialylation. Statistical significance was reached for presence of galectin-3, found to be elevated in microsatellite-stable compared to microsatellite-unstable tumors. These results emphasize the potential of distinct signaling pathways to regulate certain aspects of the glycophenotype in vivo and thus delineate a perspective to discern functionally relevant deviations in expression of endogenous lectins and their counter-receptors.
authors.affiliation: Abteilung Angewandte Tumorbiologie, Universitaetsklinikum Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gebert
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.forename: Michaela
authors.initials: M
authors.lastname: Lohr
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Rudolf
authors.initials: R
authors.lastname: Wagner
authors.forename: Juergen
authors.initials: J
authors.lastname: Kopitz
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D037161:Galectins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D053842:Microsatellite Instability; D010641:Phenotype; D037121:Plant Lectins / Q000378:metabolism; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism*
chemical_list: D037161:Galectins; D037121:Plant Lectins; D011134:Polysaccharides