gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

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Secretion and Uptake of Recombinant GBP-1: A New Approach for an Anti-Angiogenic Tumor Therapy

Meeting Abstract

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  • corresponding author presenting/speaker Mirjam Metzner - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Deutschland
  • Mike Hupe - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen
  • Elisabeth Naschberger - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen
  • Mathias Thurau - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen
  • Christine Hohenadl - AUSTRIANOVA Biotechnology GmbH , Wien
  • Karoline Lipnik - Research Institute for Virology and Biomedicine, University of Veterinary Medicine, Wien
  • Thomas Mörtinger - Research Institute for Virology and Biomedicine, University of Veterinary Medicine, Wien
  • Werner Hohenberger - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen
  • Michael Stürzl - Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen-Nuremberg, Erlangen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO473

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk583.shtml

Veröffentlicht: 20. März 2006

© 2006 Metzner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

Tumor growth depends on the formation of new blood vessels. The inhibition of angiogenesis therefore represents a possible strategy for tumor therapy. Expression of guanylate binding protein-1 (GBP-1) characterizes inflammatory cytokine (IC)-activated endothelial cells (EC). In addition, GBP-1 mediates the anti-angiogenic effects of IC on EC, inhibiting EC proliferation, migration and invasion. In this approach we are evaluating the use of GBP-1 as a therapeutic gene for an anti-angiogenic tumor therapy. Retroviral vectors will be employed to express GBP-1 in tumor lesions. To amplify the anti-angiogenic potential of GBP-1, recombinant GBP-1 will be provided with a multi-signaling motif facilitating release from infected cells, uptake by non-infected neighboring cells and allowing immunochemical detection. For optimization of the multi-signaling motif we used GFP as reporter protein. Analysis of various combinations of different signaling elements revealed that the export signal sequence of the human extracellular matrix protein osteonectin (Ost), the basic poly-lysine transduction peptide (Lys) and the artificial Flag-tag (Flag) are most effective to facilitate secretion, uptake and immunochemical detection of the modified protein. In addition, introduction of a glycine-linker (G) following the Ost sequence clearly increased secretion efficiencies. We could show that the final product Ost-G-Lys-G-Flag-GFP is highly expressed and efficiently secreted by HEK293T cells as well as efficiently incorporated by HeLa cells. In a next step GFP was replaced by GBP-1. Expression and secretion of the modified recombinant GBP-1 protein could already be demonstrated. Ongoing studies will evaluate the beneficial effects of this approach on the anti-angiogenic efficacy of GBP-1.