TY - JOUR
T1 - Insulin-like growth factor-binding protein 7 alters the sensitivity to interferon-based anticancer therapy in hepatocellular carcinoma cells
AU - Tomimaru, Y.
AU - Eguchi, H.
AU - Wada, H.
AU - Noda, T.
AU - Murakami, M.
AU - Kobayashi, S.
AU - Marubashi, S.
AU - Takeda, Y.
AU - Tanemura, M.
AU - Umeshita, K.
AU - Doki, Y.
AU - Mori, M.
AU - Nagano, H.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/5
Y1 - 2010/5
N2 - Background:A striking efficiency of interferon (IFN)-based anticancer therapy for advanced hepatocellular carcinoma (HCC) has been reported. Because its clinical efficiency greatly depends on each patient's local response, prediction of local response is crucial.Methods:Continuous exposure of IFN-α to parental PLC/PRF/5 cells (PLC-P) and a limiting dilution method resulted in the establishment of IFN-resistant cell clones (PLC-Rs). Microarray analyses of PLC-P and PLC-Rs identified insulin-like growth factor-binding protein 7 (IGFBP7) as one of the most significantly downregulated genes in PLC-Rs. Changes in anticancer effects of IFN-α were examined in HCC cells after genetic manipulation of IGFBP7 expression. The correlation between immunohistochemically determined IGFBP7 expression and the response to IFN-α/5-fluorouracil (5-FU) therapy was investigated in surgically resected HCC specimens.Results:PLC-R cells showed a remarkable downregulation of IGFBP7 and resistance to IFN-α, compared with PLC-P. Parental PLC/PRF/5 cells transfected with short hairpin RNA against IGFBP7 showed a significant resistance to IFN-α relative to control cells (IC 50 fold increase14.38 times). Insulin-like growth factor-binding protein 7 transfection into PLC-R restored sensitivity to IFN-α. In resected specimens, IGFBP7 expression significantly correlated with the response to IFN-α/5-FU therapy.Conclusion:IGFBP7 could be a useful predictor of the response to IFN-based therapy in advanced HCC.
AB - Background:A striking efficiency of interferon (IFN)-based anticancer therapy for advanced hepatocellular carcinoma (HCC) has been reported. Because its clinical efficiency greatly depends on each patient's local response, prediction of local response is crucial.Methods:Continuous exposure of IFN-α to parental PLC/PRF/5 cells (PLC-P) and a limiting dilution method resulted in the establishment of IFN-resistant cell clones (PLC-Rs). Microarray analyses of PLC-P and PLC-Rs identified insulin-like growth factor-binding protein 7 (IGFBP7) as one of the most significantly downregulated genes in PLC-Rs. Changes in anticancer effects of IFN-α were examined in HCC cells after genetic manipulation of IGFBP7 expression. The correlation between immunohistochemically determined IGFBP7 expression and the response to IFN-α/5-fluorouracil (5-FU) therapy was investigated in surgically resected HCC specimens.Results:PLC-R cells showed a remarkable downregulation of IGFBP7 and resistance to IFN-α, compared with PLC-P. Parental PLC/PRF/5 cells transfected with short hairpin RNA against IGFBP7 showed a significant resistance to IFN-α relative to control cells (IC 50 fold increase14.38 times). Insulin-like growth factor-binding protein 7 transfection into PLC-R restored sensitivity to IFN-α. In resected specimens, IGFBP7 expression significantly correlated with the response to IFN-α/5-FU therapy.Conclusion:IGFBP7 could be a useful predictor of the response to IFN-based therapy in advanced HCC.
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U2 - 10.1038/sj.bjc.6605669
DO - 10.1038/sj.bjc.6605669
M3 - Article
C2 - 20407444
AN - SCOPUS:77952242309
SN - 0007-0920
VL - 102
SP - 1483
EP - 1490
JO - British journal of cancer
JF - British journal of cancer
IS - 10
ER -
