Saracatinib impairs the peritoneal dissemination of diffuse-type gastric carcinoma cells resistant to Met and fibroblast growth factor receptor inhibitors.
Bottom Line: A Src inhibitor saracatinib impaired growth in cell lines that are insensitive to both Met and FGFR2 inhibitors.Saracatinib also effectively impaired peritoneal dissemination of Met-independent and FGFR2-independent SGC cells.Moreover, DGC cell lines exhibited nearly mutually exclusive susceptibility to Met, FGFR and Src inhibitors.
Affiliation: Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.Show MeSH
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Mentions: The effects of several inhibitors targeted to signaling molecules other than Met were then examined. PD-173074, a pan-FGFR inhibitor, treatment strongly inhibited the growth of KATO-III and HSC-39 and moderately inhibited HSC-43 and HSC-64 (Fig.3a). These sensitive cell lines displayed increased phosphorylation of FRS2α, an adaptor protein for FGFR (Fig.3b). KATO-III and HSC-43 cells also showed robust overexpression and phosphorylation of FGFR2α, which is consistent with k-sam amplification in those cell lines.36 It is unclear why FGFR2α expression was not detected in HSC-39 cells, which also have k-sam amplification.36 Taken together, phosphorylation of FRS2α and overexpression of FGFR2α seem to be correlated with sensitivity to FGFR inhibition.
Affiliation: Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.