Abstract
Purpose:
There is no established adjuvant or neo-adjuvant treatment to curb tumor recurrence of hepatocellular carcinoma (HCC). Recent data showed that angiostatic factors can inhibit tumor cell adhesion to the endothelium and therefore recurrence/metastasis. We tested a potential preventive, pre-operative strategy using plasminogen kringles 1-3 (K1-3) to overcome this hurdle.
Materials and methods:
Effects of K1-3 on the intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) expression was analyzed in vitro and in vivo on RNA and protein levels. Influence of K1-3 on HCC recurrence in the liver was analyzed in an orthotopic tumor model.
Results:
K1-3 decreased ICAM expression in Hepa129 tumor cells and VCAM expression in SVEC4-10 endothelial cells in vitro. In vivo, ICAM was reduced in histological tumor sections. Preventive treatment with AdK1-3 inhibited experimental HCC recurrence and tumor growth in the liver.
Conclusions:
We were able to show that K1-3 inhibits intrahepatic tumor recurrence. This novel aspect elucidates a possible approach to prevent HCC recurrence.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Angiogenesis Inhibitors / pharmacology
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Animals
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Genetic Vectors / genetics
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Humans
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Kringles*
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Liver Neoplasms, Experimental / enzymology
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Liver Neoplasms, Experimental / genetics
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Liver Neoplasms, Experimental / metabolism*
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Liver Neoplasms, Experimental / pathology
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Male
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Matrix Metalloproteinase 9 / metabolism
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Mice
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Neoplasm Metastasis
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Peptide Fragments / pharmacology*
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Plasminogen / pharmacology*
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Recurrence
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Angiogenesis Inhibitors
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Cell Adhesion Molecules
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Peptide Fragments
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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Plasminogen
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Matrix Metalloproteinase 9