Skip Navigation



Carcinogenesis Advance Access published online on February 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp052
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/5/851    most recent
bgp052v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Persano, L.
Right arrow Articles by Amadori, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Persano, L.
Right arrow Articles by Amadori, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Interferon-{alpha} Counteracts the Angiogenic Switch and Reduces Tumor Cell Proliferation in a Spontaneous Model of Prostatic Cancer

Luca Persano1, Lidia Moserle1, Giovanni Esposito2, Vincenzo Bronte2, Vito Barbieri1, Massimo Iafrate3, Marina Paola Gardiman4, Patrizia Larghero5, Ulrich Pfeffer5, Elisabeth Naschberger6, Michael Stürzl6, Stefano Indraccolo2 and Alberto Amadori1,2

1 Oncology Section, Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy
2 Istituto Oncologico Veneto - IRCCS, Padova, Italy
3 Urology Section, Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy
4 Pathology Unit, Azienda Ospedaliera, Padova, Italy
5 Functional Genomics, National Cancer Research Institute, Genova, Italy
6 Department of Surgery, Division of Molecular and Experimental Surgery, Erlangen, Germany

Corresponding Author: Stefano Indraccolo, M.D., Istituto Oncologico Veneto, IRCCS, via Gattamelata, 64, 35128 PADOVA – ITALY, Ph. ++39-0498215875; Fax ++30-0498072854, e-mail: stefano.indraccolo{at}unipd.it

Interferon-{alpha} (IFN-{alpha}) is a cytokine with marked therapeutic activity in transplantable tumor models, that is in part due to angiogenesis inhibition. Aim of this study was to investigate the effects of IFN-{alpha} during the early phases of tumor development in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. To provide sustained IFN-{alpha} production, TRAMP mice were injected i.p. with lentiviral vectors. IFN-{alpha} administration resulted in rapid and protracted up-regulation of IFN-{alpha}-regulated genes associated with anti-angiogenic and anti-proliferative functions in the prostate of TRAMP mice, including guanylate binding protein 1 (GBP-1), IFI204 and CXCL10-11. These transcriptional changes were accompanied by effects on the tumor vasculature, including significant reduction of intraductal microvessel density and increased pericyte coverage, and marked reduction of tumor cell proliferation, without induction of tumor necrosis. Intriguingly, GBP-1 and MxA, two IFN-regulated proteins, were found expressed in about 40% of human prostate cancer samples analyzed, suggesting expression of endogenous IFN-{alpha}. Overall, these findings demonstrate that IFN-{alpha} is able to counteract the angiogenic switch and impairs tumor cell proliferation in pre-invasive lesions. Since the angiogenic switch also marks progression of human prostatic cancer, these results highlight the potential of angiogenesis inhibitors for the development of chemoprevention strategies in high-risk individuals.

Key Words: prostatic cancer • TRAMP model • interferon • angiogenesis • GBP-1

Received October 21, 2008; revised February 3, 2009; accepted February 4, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.