Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

Liver resection-associated macrophage inflammatory protein-2 stimulates engraftment but not growth of colorectal metastasis at extrahepatic sites.

Kollmar O, Junker B, Rupertus K, Scheuer C, Menger MD, Schilling MK

Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany. otto.kollmar@uniklinikum-saarland.de

BACKGROUND: Previous studies have shown that liver resection enhances intrahepatic engraftment of CXCR-2-expressing colorectal cancer cells by the action of the CXC chemokine macrophage inflammatory protein (MIP)-2. Herein we studied how liver resection-associated MIP-2 affects extrahepatic tumor cell engraftment and whether MIP-2 also stimulates the growth of already established metastases. MATERIALS AND METHODS: Green fluorescent protein-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Additionally, all animals underwent a 30% hepatectomy. To study MIP-2 in extrahepatic tumor cell engraftment, animals were treated with an anti-MIP-2 antibody, starting at the day of tumor cell implantation. To study MIP-2 in established metastases, anti-MIP-2 treatment was initiated at day 5 after tumor cell implantation. Hepatectomized animals without neutralization of MIP-2 served as controls. Tumor vascularization and growth as well as tumor cell migration, proliferation, apoptosis, and CXCR-2 expression were studied over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. RESULTS: Functional inhibition of MIP-2 significantly delayed extrahepatic tumor cell engraftment but not the growth of established metastases. The initial delay of engraftment was associated with a compensatory stimulation of vascularization and tumor cell migration when compared to controls (P < 0.05). Further, inhibition of tumor cell engraftment by initial anti-MIP-2 treatment was associated with a significant (P < 0.05) reduction of CXCR-2 expression and tumor cell apoptosis. CONCLUSION: Our study indicates that MIP-2 is involved in extrahepatic engraftment of CT.26 colorectal cancer cells. The MIP-2/CXCR-2 signaling pathway may be a promising target for early antitumor therapy in patients undergoing liver resection.

Published 10 March 2008 in J Surg Res, 145(2): 295-302.
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