Journal of Translational Medicine
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.
CONCLUSION: 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.
Apoptosis, Cell Count, Cell Cycle, Cell Line, Tumor, Cell Movement, Cell Proliferation, Humans, Indoles, Intracellular Space, Phosphorylation, Piperazines, Protein Kinase Inhibitors, Protein Transport, Proto-Oncogene Proteins c-met, Rhabdomyosarcoma, Signal Transduction, Small Molecule Libraries, Sulfonamides
This work is licensed under a Creative Commons Attribution 2.0 License. Creative Commons Attribution License 2.0
Hou, Jinxuan; Dong, Jixin; Sun, Lijun; Geng, Liying; Wang, J.; Zheng, Jialin C.; Li, Yan; Bridge, Julia A.; Hinrichs, Steven H.; and Ding, Shi-Jian, "Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274." (2011). Journal Articles: Pathology and Microbiology. 26.