title: GBP-1 acts as a tumor suppressor in colorectal cancer cells.
abstract: The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by interferon-γ (IFN-γ) in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cancer. In colorectal carcinoma (CRC), the expression of GBP-1 in the desmoplastic stroma has been previously reported to correlate with the presence of an IFN-γ-dominated T helper type 1 (Th1) micromilieu and with an increased cancer-related 5-year survival. In the present study, the analysis of GBP-1 expression in a series of 185 CRCs by immunohistochemistry confirmed that GBP-1 is expressed in stroma cells of CRCs and revealed a significantly less frequent expression in tumor cells, which was contradictory with the broad inducibility of GBP-1. Furthermore, three of six CRC cell lines treated with IFN-γ were unable to express GBP-1 indicating that colorectal tumor cells tend to downregulate GBP-1. On the contrary, non-transformed colon epithelial cells strongly expressed GBP-1 in vitro in presence of IFN-γ and in vivo in inflammatory bowel diseases. Reconstitution of GBP-1 expression in a negative CRC cell line inhibited cell proliferation, migration and invasion. Using RNA interference, we showed that GBP-1 mediates the antitumorigenic effects of IFN-γ in CRC cells. In addition, GBP-1 was able to inhibit tumor growth in vivo. Altogether, these results suggested that GBP-1 acts directly as a tumor suppressor in CRC and the loss of GBP-1 expression might indicate tumor evasion from the IFN-γ-dominated Th1 immune response.
authors.affiliation: Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Schwabachanlage 10,  91054 Erlangen, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Britzen-Laurent
authors.forename: Karoline
authors.initials: K
authors.lastname: Lipnik
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
authors.forename: Vera S
authors.initials: VS
authors.lastname: Schellerer
authors.forename: Roland S
authors.initials: RS
authors.lastname: Croner
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.forename: Maximilian
authors.initials: M
authors.lastname: Waldner
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
authors.forename: Christine
authors.initials: C
authors.lastname: Hohenadl
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D034622:RNA Interference
chemical_list: C490287:GBP1 protein, human; D019204:GTP-Binding Proteins