title: Isolation of a human gallbladder cancer cell clone with high invasive phenotype in vitro and metastatic potential in orthotopic model and inhibition of its invasiveness by heparanase antisense oligodeoxynucleotides.
abstract: The mechanisms involved in gallbladder cancer metastasis still remain unclear to date. The poor understanding is due, in part, to the lack of ideal cell line and animal model for study. In the present study, 21 cell clones were isolated from the human gallbladder carcinoma cells GBC-SD and the cell clone GBC-SDH(i) with high invasive phenotype was fished out. The invasive phenotype and metastatic potential of GBC-SDH(i) were confirmed in a novel surgical orthotopic implantation model of gallbladder cancer in nude mice. Heparanase, an endoglycosidase that degrades heparan sulfate, is a critical mediator of tumor metastasis and angiogenesis. RT-PCR, real time RT-PCR and western blot showed that the expression levels of heparanase were significant difference between GBC-SDH(i) and its parent cells. After treated with antisense oligodeoxynucleotides, the heparanase mRNA and protein expression in GBC-SDH(i) cells were significantly decreased and its invasive potential in vitro was inhibited in a dose-dependent manner. The study provides a useful cell clone and a clinically relevant orthotopic tumor model for the metastatic study in human gallbladder cancer. The roles of heparanase in gallbladder cancer are also evaluated.
authors.affiliation: Central Laboratory, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Xin-Zhong
authors.initials: XZ
authors.lastname: Chang
authors.forename: Zhan-Min
authors.initials: ZM
authors.lastname: Wang
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yu
authors.forename: Fu-Guo
authors.initials: FG
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Lian-Fang
authors.initials: LF
authors.lastname: Li
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Liu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002999:Clone Cells; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000473:pathology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D016376:Oligonucleotides, Antisense; D000099175:Heparanase