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

Abstract

Several recent studies have reported that selectins are produced during ischemia-reperfusion injury, and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis.

• Authors: Katsuhiro Yoshimoto, Hidehiro Tajima, Tetsuo Ohta, Koichi Okamoto, Seisho Sakai, Jun Kinoshita, Hiroyuki Furukawa, Isamu Makino, Hironori Hayashi, Keishi Nakamura, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Hiroshi Itoh, Hideto Fujita, Hiroyuki Takamura, Itasu Ninomiya, Hirohisa Kitagawa, Sachio Fushida, Takashi Fujimura, Tomohiko Wakayama, Shoichi Iseki, Koichi Shimizu
• Journal: Oncology reports (Oncol Rep) Vol. 28 Issue 3 Pg. 791-6 (Sep 2012) ISSN: 1791-2431 [Electronic] Greece
• PMID: 22766603 (Publication Type: Journal Article)

Chemical References

• E-Selectin
• Interleukin-1
• Tumor Necrosis Factor-alpha

Topics

• Adenocarcinoma (etiology, metabolism, secondary)
• Adult
• Animals
• Cell Line, Tumor
• E-Selectin (genetics, metabolism)
• Gene Expression
• Humans
• Interleukin-1 (genetics, metabolism)
• Liver Neoplasms (etiology, metabolism, secondary)
• Male
• Mice
• Mice, Inbred ICR
• Mice, Nude
• Neoplasm Transplantation
• Pancreatic Neoplasms (etiology, metabolism, pathology)
• Reperfusion Injury (complications, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)