title: Osteopontin promotes hepatocellular carcinoma invasion by up-regulating MMP-2 and uPA expression.
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.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
authors.forename: Rong-Xin
authors.initials: RX
authors.lastname: Chen
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Xia
authors.forename: Tong-Chun
authors.initials: TC
authors.lastname: Xue
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Ye
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002999:Clone Cells; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D053495:Osteopontin; C059485:matrigel; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2