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Naschberger, E.* ; Croner, R.S.* ; Merkel, S.* ; Dimmler, A.* ; Tripal, P.* ; Amann, K.U.* ; Kremmer, E. ; Brueckl, W.M.* ; Papadopoulos, T.* ; Hohenadl, C.* ; Hohenberger, W.* ; Stürzl, M.*

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

Int. J. Cancer 123, 2120-2129 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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-gamma-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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter guanylate binding protein-1; interferon-gamma; colorectal carcinoma; angiogenesis; inflammation
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Zeitschrift International Journal of Cancer
Quellenangaben Band: 123, Heft: 9, Seiten: 2120-2129 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)