Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth.
OBJECTIVE
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, 1x10(5) 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.


CONCLUSIONS
MIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.
Kollmar
Otto
O
Department of General, Visceral, Vascular and Pediatric Surgery, University of the Saarland, D-66421 Homburg/Saar, Germany. chokol@uniklinik-saarland.de
Menger
Michael D
MD
Schilling
Martin K
MK
D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002455:Cell Division; D054426:Chemokine CXCL2; D015179:Colorectal Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary* / Q000601:surgery* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000473:pathology; D015846:Monokines / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D054426:Chemokine CXCL2; D015846:Monokines