Macrophage inflammatory protein-2 contributes to liver resection-induced acceleration of hepatic metastatic tumor growth.

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, 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.

CONCLUSION

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