Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 14, 2006; 12(6): 858-867
Published online Feb 14, 2006. doi: 10.3748/wjg.v12.i6.858
Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth
Otto Kollmar, Michael D Menger, Martin K Schilling
Otto Kollmar, Martin K Schilling, Department of General, Visceral, Vascular and Pediatric Surgery, University of the Saarland, D-66421 Homburg/Saar, Germany
Michael D Menger, Institute for Clinical and Experimental Surgery, University of the Saarland, D-66421 Homburg/Saar, Germany
Supported by the grants of the Research Committee and the Medical Faculty of the University of Saarland, No. HOMFOR-A/2003/1
Correspondence to: Otto Kollmar, MD, Department of General, Visceral, Vascular and Pediatric Surgery, University of the Saarland, D-66421 Homburg/Saar, Germany. chokol@uniklinik-saarland.de
Telephone: +49-6841-1622611 Fax: +49-6841-1622697
Received: July 22, 2005
Revised: August 5, 2005
Accepted: August 26, 2005
Published online: February 14, 2006
Abstract

AIM: To study the role of macrophage inflammatory protein (MIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis.

METHODS: After a 50% hepatectomy, 1×105 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (MAB452) neutralizing MIP-2 (PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using intravital fluorescence microscopy, histology, immunohistochemistry, and flow cytometry.

RESULTS: Partial hepatectomy increased (P < 0.05) the expression of the MIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P < 0.05) angiogenesis and metastatic tumor growth. Neutralization of MIP-2 by MAB452 treatment significantly (P < 0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P < 0.05) and inhibited tumor growth (P < 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-MIP-2 treatment.

CONCLUSION: MIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.

Keywords: Chemokines, MIP-2, Liver resection, Partial hepatectomy, Liver regeneration, Metastatic tumor growth, Angiogenesis, Microcirculation