title: Galectin-9: An anticancer molecule for gallbladder carcinoma.
abstract: Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeat-type galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tadokoro
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Asahiro
authors.initials: A
authors.lastname: Morishita
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fujihara
authors.affiliation: Life Science Research Center, Kagawa University, Kagawa, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Kagawa, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Akashi
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Shima
authors.initials: S
authors.lastname: Mimura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Oura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Tani
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yoneyama
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Himoto
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Kagawa, Japan.
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.affiliation: Department of Gastroenterology and Neurology, Kagawa University, Kagawa, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D037161:Galectins / Q000378:metabolism*; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D023041:Xenograft Model Antitumor Assays
chemical_list: D037161:Galectins; D053538:Keratin-18; C105032:LGALS9 protein, human; D035683:MicroRNAs