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LIM kinase‐2 targeting as a possible anti‐metastasis therapy
Author(s) -
Suyama Eigo,
Wadhwa Renu,
Kawasaki Hiroaki,
Yaguchi Tomoko,
Kaul Sunil C.,
Nakajima Motowo,
Taira Kazunari
Publication year - 2004
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.491
Subject(s) - fibrosarcoma , ribozyme , cancer research , biology , cell migration , cell , microbiology and biotechnology , ht1080 , rna , biochemistry , genetics , gene
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. Copyright © 2004 John Wiley & Sons, Ltd.