RRC ID 43350
Author Tamagawa K, Horiuchi T, Uchinami M, Doi K, Yoshida M, Nakamura T, Sasaki H, Taniguchi M, Tanaka K.
Title Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats.
Journal J. Surg. Res.
Abstract BACKGROUND:In liver surgery, the hepatic pedicle often is clamped to reduce blood loss, and later unclamped, representing hepatic ischemia and reperfusion (I/R) with induction of hypoxia. Vascular endothelial growth factor (VEGF) expression reportedly is induced by hypoxia; further, some cancer cells express the VEGF receptor (flt-1, flk-1/KDR). We hypothesized that I/R-induced VEGF expression could enhance growth of microscopic tumor via VEGF receptors on tumor cells, thus promoting liver metastasis in a rat model.
MATERIALS AND METHODS:Time-dependent VEGF expression in liver and plasma was determined by enzyme-linked immunosorbent assay in rats subjected to 60 min of 70% hepatic I/R (I/R group). Other rats given an intrasplenic inoculation of a rat colon adenocarcinoma cell line (RCH-H4) were divided 3 days later into three groups: group A, untreated; group B, sham operation; group C, 70% I/R for 60 min. Liver metastasis was evaluated on day 14. Expression of flt-1 and flk-1/KDR was examined in RCN-H4 cells, and effects of exogenous VEGF on RCN-H4 cell proliferation were determined by MTT assays.
RESULTS:Hepatic VEGF expression increased significantly in the I/R group compared to the control group. Liver metastasis was more extensive in group C than in groups A and B. RCN-H4 cells expressed flt-1 and flk-1/KDR, while exogenous VEGF increased RCN-H4 cell proliferation.
CONCLUSION:Hepatic ischemia reperfusion leads to induction of VEGF and this is associated with increased tumor burden in an animal model of colon cancer metastasis.
Volume 148(2)
Pages 158-63
Published 2008-8
DOI 10.1016/j.jss.2007.12.787
PII S0022-4804(07)02433-X
PMID 18468635
MeSH Adenocarcinoma / pathology* Alanine Transaminase / metabolism Animals Aspartate Aminotransferases / metabolism Cell Line, Tumor Colonic Neoplasms / pathology* Disease Models, Animal Gene Expression Regulation, Neoplastic Liver / enzymology Liver Neoplasms / physiopathology* Liver Neoplasms / secondary* Male Rats Rats, Inbred F344 Reperfusion Injury / physiopathology* Vascular Endothelial Growth Factor A / metabolism* Vascular Endothelial Growth Factor Receptor-1 / metabolism Vascular Endothelial Growth Factor Receptor-2 / metabolism
IF 1.872
Times Cited 17
Human and Animal Cells