Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer

Several recent studies have reported that selectins are produced duringischemia-reperfusion injury, and that selectin ligands play an important rolein cell binding to the endothelium and in liver metastasis. Portal clamping duringpancreaticoduodenectomy with vessel resection for pancreatic head cancer causeshepatic ischemia-reperfusion injury, which might promote liver metastasis. Weinvestigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusionand examined the involvement of E-selectin and its ligands. A human pancreaticcancer cell line (Capan-1) was injected into the spleen of mice after hepaticischemia-reperfusion (I/R group). In addition, to investigate the effect of ananti-E-selectin antibody on liver colonization in the IR group, mice receivedan intraperitoneal injection of the anti-E-selectin antibody following hepaticischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, micewere sacrificed and the number of tumor nodules on the liver was compared to micewithout hepatic ischemia-reperfusion (control group). The incidence of liver metastasisin the I/R group was significantly higher (16 of 20, 80%) than that in the controlgroup (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantlymore tumor nodules compared to those in the control group (median, 9.9 vs. 2.7nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed livermetastases. RT-PCR and southern blotting of the liver extracts showed that theexpression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion wassignificantly higher than the basal levels. Hepatic ischemia-reperfusion increasesliver metastases and E-selectin expression in pancreatic cancer. These resultssuggest that E-selectin produced due to hepatic ischemia-reperfusion is involvedin liver metastasis.