GBP-1 acts as a tumor suppressor in colorectal cancer cells

Britzen-Laurent N, Lipnik K, Ocker M, Naschberger E, Schellerer V, Croner RS, Vieth M, Waldner M, Steinberg P, Hohenadl C, Stürzl M (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Book Volume: 34

Pages Range: 153-162

Journal Issue: 1

DOI: 10.1093/carcin/bgs310

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. © The Author 2012. Published by Oxford University Press. All rights reserved.

Authors with CRIS profile

Involved external institutions

Stiftung Tierärztliche Hochschule Hannover (TiHo) Germany (DE) Veterinärmedizinische Universität Wien (Vetmeduni Vienna) / University of Veterinary Medicine, Vienna Austria (AT) Philipps-Universität Marburg Germany (DE)

How to cite

APA:

Britzen-Laurent, N., Lipnik, K., Ocker, M., Naschberger, E., Schellerer, V., Croner, R.S.,... Stürzl, M. (2013). GBP-1 acts as a tumor suppressor in colorectal cancer cells. Carcinogenesis, 34(1), 153-162. https://doi.org/10.1093/carcin/bgs310

MLA:

Britzen-Laurent, Nathalie, et al. "GBP-1 acts as a tumor suppressor in colorectal cancer cells." Carcinogenesis 34.1 (2013): 153-162.

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