title: Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential.
abstract: OBJECTIVE
  We recently reported a protective role of clusterin expression against apoptosis induced by a wide variety of stimuli in several human cancer models. In the current study we tested the hypothesis that clusterin over expression confers a benefit for the metastasis of renal cell carcinoma through the inhibition of apoptosis induced by the various obstacles the cancer cells may confront after detachment from their primary origin.
  
  
  METHODS
  We introduced clusterin complementary DNA into human renal cell carcinoma ACHN cells, which do not express detectable level of clusterin expression, and generated the clusterin over expressing cell line ACHN/CL and the control vector only transfected cell line ACHN/C. In vitro anti-cell death activity under anchorage independent conditions among ACHN sublines was examined by limiting dilution assay and cell survival assay in suspension. To investigate the in vivo effects of clusterin over expression on metastatic potentials each cell line was injected into the tail vein or renal subcapsule of nonobese diabetic, severe combined immunodeficient mice and the metastatic features in all abdominal and thoracic organs were evaluated.
  
  
  RESULTS
  ACHN/CL showed significantly enhanced growth in limiting dilution cultures compared with ACHN/C. The analysis of cell survival in the floating assay also revealed that ACHN/CL had a powerful survival advantage in suspension compared with ACHN/C. Furthermore, ACHN/CL formed more than 5-fold as many metastatic nodules in the lung after intravenous injection than ACHN/C. Similarly more marked lung metastasis was observed after implanting ACHN/CL cells into the renal subcapsule than after implanting ACHN/C cells. In contrast, there were no significant differences among ACHN sublines in the growth rates in vitro and in vivo, cell motility or invasive ability.
  
  
  CONCLUSIONS
  These findings suggest that, if clusterin is over expressed, it prolongs cell survival under unfavorable conditions in the metastatic process, resulting in the enhanced metastatic potential of renal cell carcinoma.
authors.affiliation: Department of Urology, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Soichi
authors.initials: S
authors.lastname: Arakawa
authors.forename: Sadao
authors.initials: S
authors.lastname: Kamidono
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D005810:Multigene Family / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger