title: LIM kinase-2 targeting as a possible anti-metastasis therapy.
abstract: BACKGROUND
  Metastatic properties of tumors involve movement of cancerous cells from one place to another and tissue invasion. Metastatic cells have altered cell adhesion and movement that can be examined by in vitro chemotaxis assays. The Rho/ROCK/LIM kinase pathway is one of the major signaling pathways involved in tumor metastasis. It is involved in the regulation of the actin cytoskeleton. Using the randomized ribozyme library, we initially found that metastatic human fibrosarcoma cells harboring ribozyme specific for ROCK lose their metastatic properties. In this study, we have determined the effect of ribozymes specific for LIM kinase-2 on metastatic and proliferative phenotypes of human fibrosarcoma cells.
  
  
  METHODS
  We attempted to target LIM kinase-2 (LIMK-2) expression by hammerhead ribozymes (Rz) in human metastatic fibrosarcoma cells. An effective ribozyme was selected based on the expression analysis. Cells were stably transfected with Rz specifically effective for LIMK-2 and were examined for metastatic and proliferative properties.
  
  
  RESULTS
  Analyses of cellular phenotypes such as cell proliferation, cell migration and colony-forming efficiency revealed that the suppression of LIMK-2 expression in human fibrosarcoma cells limits their migration and dense colony-forming efficiency without affecting cell proliferation rate or viability.
  
  
  CONCLUSIONS
  Specific targeting of metastatic and malignant properties of tumor cells by LIMK-2 ribozyme may serve as an effective therapy for invasive tumors with minimum effect on the surrounding normal cells.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Suyama
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D054461:Lim Kinases; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009362:Neoplasm Metastasis / Q000628:therapy*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D012366:RNA, Transfer, Val / Q000235:genetics; D014410:Tumor Stem Cell Assay
chemical_list: D004268:DNA-Binding Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012366:RNA, Transfer, Val; C427204:hammerhead ribozyme; C102895:LIMK2 protein, human; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases