title: Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase.
abstract: Sialic acids are acidic monosaccharides that bind to the sugar chains of glycoconjugates and change their conformation, intermolecular interactions, and/or half-life. Thus, sialidases are believed to modulate the function of sialoglycoconjugates by desialylation. We previously reported that the membrane-associated mammalian sialidase NEU3, which preferentially acts on gangliosides, is involved in cell differentiation, motility, and tumorigenesis. The NEU3 gene expression is aberrantly elevated in several human cancers, including colon, renal, prostate, and ovarian cancers. The small interfering RNA-mediated knock-down of NEU3 in cancer cell lines, but not in normal cell-derived primary cultures, downregulates EGFR signaling and induces apoptosis. Here, to investigate the physiological role of NEU3 in tumorigenesis, we established Neu3-deficient mice and then subjected them to carcinogen-induced tumorigenesis, using a sporadic and a colitis-associated colon cancer models. The Neu3-deficient mice showed no conspicuous accumulation of gangliosides in the brain or colon mucosa, or overt abnormalities in their growth, development, behavior, or fertility. In dimethylhydrazine-induced colon carcinogenesis, there were no differences in the incidence or growth of tumors between the Neu3-deficient and wild-type mice. On the other hand, the Neu3-deficient mice were less susceptible than wild-type mice to the colitis-associated colon carcinogenesis induced by azoxymethane and dextran sodium sulfate. These results suggest that NEU3 plays an important role in inflammation-dependent tumor development.
authors: Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan. kyamaguchi@med.tohoku.ac.jp
authors: Kazunori
authors: K
authors: Yamaguchi
authors: Kazuhiro
authors: K
authors: Shiozaki
authors: Setsuko
authors: S
authors: Moriya
authors: Koichi
authors: K
authors: Koseki
authors: Tadashi
authors: T
authors: Wada
authors: Hiroo
authors: H
authors: Tateno
authors: Ikuro
authors: I
authors: Sato
authors: Masahide
authors: M
authors: Asano
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Taeko
authors: T
authors: Miyagi
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000737:chemistry; D002462:Cell Membrane / Q000201:enzymology; D003092:Colitis / Q000209:etiology* / Q000235:genetics*; D003110:Colonic Neoplasms / Q000209:etiology* / Q000235:genetics*; D003911:Dextrans / Q000737:chemistry; D005732:Gangliosides / Q000737:chemistry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D005838:Genotype; D006001:Glycoconjugates / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics; D012794:Sialic Acids / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry
chemical_list: D003911:Dextrans; D005732:Gangliosides; D006001:Glycoconjugates; D006017:Glycolipids; D012794:Sialic Acids; D013431:Sulfates; C012036:sodium sulfate; C511796:Neu3 protein, mouse; D009439:Neuraminidase; D001397:Azoxymethane