title: Lentivirus-mediated RNA silencing of c-Met markedly suppresses peritoneal dissemination of gastric cancer in vitro and in vivo.
abstract: OBJECTIVE
  To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer.
  
  
  METHODS
  Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PFCCs was detected with immunocytochemistry. In human gastric cancer cell line SGC7901, c-Met expression was detected using RT-PCR and Western blot, and was suppressed with lentivirus-mediated RNAi. The proliferation of SGC7901 cells was measured using MTT assay, and the invasion ability was detected with invasion assay. The adhesion of SGC7901 cells to peritoneum was observed in human peritoneal mesothelial cells (HPMCs) monolayer in vitro and in mice in vivo.
  
  
  RESULTS
  PFCCs were isolated from ascites of 6 out of 10 gastric cancer patients. c-Met expression in PFCCs was detected in 5 of the 6 gastric cancer patients. In SGC7901 cells, Lentivirus-mediated RNAi significantly reduced both c-Met mRNA and protein expression, which resulted in suppressing the cell proliferation, invasion and adhesion to peritoneum. The expression of α3β1 integrin and E-cadherin was significantly inhibited in SGC7901 cells transfected with Lenti-miRNAc-Met. In the peritoneal dissemination model of gastric cancer, intraperitoneal injection of Lenti-miRNAc-Met markedly suppressed the tumor Progression of SGC7901 cells.
  
  
  CONCLUSIONS
  c-Met is expressed in PFCCs from the ascites of gastric cancer patients. Down-regulation of c-Met expression markedly suppresses the multistep process of peritoneal dissemination, thus may be a potential target for the treatment of gastric cancer.
authors.affiliation: Department of Gastroenterology, Institute of Digestive Disease, Tongji Hospital affiliated to Tongji University, Shanghai, China. xlwang2006@163.com
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Wang
authors.forename: Xi-mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Fang
authors.forename: Chang-qin
authors.initials: CQ
authors.lastname: Yang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000517:prevention & control; D010537:Peritoneum / Q000166:cytology* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D034622:RNA Interference; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D019859:Proto-Oncogene Proteins c-met