Interferon γ-Induced human guanylate binding protein 1 inhibits mammary tumor growth in mice
Lipnik K, Naschberger E, Britzen-Laurent N, Kodajova P, Petznek H, Rungaldier S, Astigiano S, Ferrini S, Stürzl M, Hohenadl C (2010)
Publication Type: Journal article
Publication year: 2010
Journal
Book Volume: 16
Pages Range: 177-187
Journal Issue: 5-6
DOI: 10.2119/molmed.2009.00172
Abstract
Interferon γ (IFN-γ) has recently been implicated in cancer immunosurveillance. Among the most abundant proteins induced by IFN-γ are guanylate binding proteins (GBPs), which belong to the superfamily of large GTPases and are widely expressed in various species. Here, we investigated whether the well-known human GBP-1 (hGBP-1), which has been shown to exert antiangio-genic activities and was described as a prognostic marker in colorectal carcinomas, may contribute to an IFN-γ-mediated tumor defense. To this end, an IFN-independent, inducible hGBP-1 expression system was established in murine mammary carcinoma (TS/A) cells, which were then transplanted into syngeneic immune-competent Balb/c mice. Animals carrying TS/A cells that had been given doxycycline for induction of hGBP-1 expression revealed a significantly reduced tumor growth compared with mock-treated mice. Immunohistochemical analysis of the respective tumors demonstrated a tightly regulated, high-level expression of hGBP-1. No signs of an enhanced immunosurveillance were observed by investigating the number of infiltrating B and T cells. However, hemoglobin levels as well as the number of proliferating tumor cells were shown to be significantly reduced in hGBP-1-expressing tumors. This finding corresponded to reduced amounts of vascular endothelial growth factor A (VEGF-A) released by hGBP-1-expressing TS/A cells in vitro and reduced VEGF-A protein levels in the corresponding mammary tumors in vivo. The results suggest that hGBP-1 may contribute to IFN-γ-mediated antitumorigenic activities by inhibiting paracrine effects of tumor cells on angiogenesis. Consequently, owing to these activities GBPs might be considered as potent members in an innate, IFN-γ-induced antitumoral defense system. © 2010 The Feinstein Institute for Medical Research.
Authors with CRIS profile
Elisabeth Naschberger
Medizinische Fakultät
Nathalie Britzen-Laurent
Professur für Molekulare und Experimentelle Chirurgie
Michael Stürzl
Professur für Molekulare und Experimentelle Chirurgie
Involved external institutions
Austria (AT)How to cite
APA:
Lipnik, K., Naschberger, E., Britzen-Laurent, N., Kodajova, P., Petznek, H., Rungaldier, S.,... Hohenadl, C. (2010). Interferon γ-Induced human guanylate binding protein 1 inhibits mammary tumor growth in mice. Molecular Medicine, 16(5-6), 177-187. https://doi.org/10.2119/molmed.2009.00172
MLA:
Lipnik, Karoline, et al. "Interferon γ-Induced human guanylate binding protein 1 inhibits mammary tumor growth in mice." Molecular Medicine 16.5-6 (2010): 177-187.
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