title: Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274.
abstract: BACKGROUND
  c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.
  
  
  METHODS
  The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle and cell migration.
  
  
  RESULTS
  A high level of phosphorylated c-Met was detected in 2 alveolar RMS cell lines (CW9019 and RH30) and 14 out of 24 RMS tissue samples, whereas relatively low levels of phospho-c-Met were observed in the embryonic RMS cell line (RD). The small molecule SU11274 could significantly reduce the phosphorylation of c-Met, resulting in inhibition of cell proliferation, G1 phase arrest of cell cycle and blocking of cell migration in CW9019 and RH30 cell lines.
  
  
  CONCLUSIONS
  These results might support the role of c-Met in the development and progression of RMS. Furthermore, the inhibitor of c-Met, SU11274, could be an effective targeting therapy reagent for RMS, especially alveolar RMS.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68105, USA.
authors.forename: Jinxuan
authors.initials: J
authors.lastname: Hou
authors.forename: Jixin
authors.initials: J
authors.lastname: Dong
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
authors.forename: Liying
authors.initials: L
authors.lastname: Geng
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jialin
authors.initials: J
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Julia
authors.initials: J
authors.lastname: Bridge
authors.forename: Steven H
authors.initials: SH
authors.lastname: Hinrichs
authors.forename: Shi-Jian
authors.initials: SJ
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C478479:((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide); D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D013449:Sulfonamides; D019859:Proto-Oncogene Proteins c-met