Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy

Naschberger E, Croner RS, Merkel S, Dimmler A, Tripal P, Amann KU, Kremmer E, Brueckl WM, Papadopoulos T, Hohenadl C, Hohenberger W, Stürzl M (2008)

Publication Type: Journal article

Publication year: 2008

Journal

Book Volume: 123

Pages Range: 2120-2129

Journal Issue: 9

DOI: 10.1002/ijc.23764

Abstract

Angiogenesis and inflammation are the 2 major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein-1 (GBP-1) is a key mediator of angiostatic effects of inflammation. Therefore, we hypothesized that GBP-1 may be a biomarker of intrinsic angiostasis associated with an improved outcome in CRC patients. GBP-1 was strongly expressed in endothelial cells and immune cells in the desmoplastic stroma of 32% of CRC as determined by immunohistochemical investigation of 388 sporadic CRC. Cancer-related 5-year survival was highly significant (p < 0.001) increased (16.2%) in patients with GBP-1-positive CRC. Multivariate analysis showed that GBP-1 is an independent prognostic factor indicating a reduction of the relative risk of cancer-related death by the half (p = 0.032). A comparative transcriptome analysis (22,215 probe sets) of GBP-1-positive (n = 12) and -negative (n = 12) tumors showed that particularly IFN-γ-induced genes including the major antiangiogenic chemokines CXCL9, CXCL10 and CXCL11 were coexpressed with GBP-1. Altogether our findings indicated that GBP-1 may be a novel biomarker and an active component of a Th-1-like angiostatic immune reaction in CRC. This reaction may affect patient's response to antiangiogenic therapy and the identification of such tumors may provide a novel criterion for patient selection. Moreover, the induction of a Th-1-like angiostatic immune reaction may be a promising approach for the clinical treatment of CRC. © 2008 Wiley-Liss, Inc.

Authors with CRIS profile

Involved external institutions

Veterinärmedizinische Universität Wien (Vetmeduni Vienna) / University of Veterinary Medicine, Vienna Austria (AT) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE)

How to cite

APA:

Naschberger, E., Croner, R.S., Merkel, S., Dimmler, A., Tripal, P., Amann, K.U.,... Stürzl, M. (2008). Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy. International Journal of Cancer, 123(9), 2120-2129. https://doi.org/10.1002/ijc.23764

MLA:

Naschberger, Elisabeth, et al. "Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy." International Journal of Cancer 123.9 (2008): 2120-2129.

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