Abstract
Osteopontin (OPN) is over-expressed in a variety of cancers, but its role in hepatocellular carcinoma (HCC) progression has not been clarified. In this study, weakly tumorigenic, non-metastastic human HCC cell line SMMC-7721 cells were forced to over-express OPN via stable transfection. A series of functional assays were performed to assess the effects of OPN on tumor cell behaviors and cDNA microarray was used to identify the genes regulated by OPN. The results showed that OPN significantly enhanced the migration and invasion of SMMC-7721 cells in vitro. In addition, CD44v6 antibody could significantly inhibit the invasion of OPN over-expressing SMMC-7721 cells. Moreover, MMP-2 and uPA expressions were significantly up-regulated in OPN over-expressing SMMC-7721 cells. Together, these findings indicate that OPN enhanced HCC cells invasion through interaction with its receptor CD44v6 and increased MMP-2 and uPA expressions, providing at least one mechanism for OPN-mediated HCC progression and metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / enzymology*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology*
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Clone Cells
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Collagen / metabolism
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Drug Combinations
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Laminin / metabolism
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Liver Neoplasms / enzymology
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology*
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Matrix Metalloproteinase 2 / genetics*
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Matrix Metalloproteinase 2 / metabolism
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Neoplasm Invasiveness
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Osteopontin / genetics
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Osteopontin / metabolism*
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Plasmids / genetics
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Proteoglycans / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Transfection
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Up-Regulation / genetics*
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Urokinase-Type Plasminogen Activator / genetics*
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Urokinase-Type Plasminogen Activator / metabolism
Substances
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Drug Combinations
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Laminin
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Proteoglycans
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RNA, Messenger
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Osteopontin
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matrigel
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Collagen
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Urokinase-Type Plasminogen Activator
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Matrix Metalloproteinase 2