Document Detail


GBP-1 acts as a tumor suppressor in colorectal cancer cells.
MedLine Citation:
PMID:  23042300     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by 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 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 IBD. 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 anti-tumorigenic 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:
Nathalie Britzen-Laurent; Karoline Lipnik; Matthias Ocker; Elisabeth Naschberger; Vera S Schellerer; Roland S Croner; Michael Vieth; Maximilian Waldner; Pablo Steinberg; Christine Hohenadl; Michael Stürzl
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-6
Journal Detail:
Title:  Carcinogenesis     Volume:  -     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, 91054, Germany.
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