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- W4361950602 abstract "<div>Abstract<p><b>Purpose:</b> Met receptor phosphorylation is associated with poor prognosis in human small cell lung cancer (SCLC). The aim of our work was to investigate the effects of hepatocyte growth factor (HGF)/Met–mediated epithelial-to-mesenchymal transition (EMT) in SCLC and to evaluate the role of Met inhibition in mesenchymal/chemorefractory SCLC models.</p><p><b>Experimental Design:</b> SCLC models of HGF-induced EMT were evaluated <i>in vitro</i> and <i>in vivo</i> (subcutaneous xenografts in BALB/c nude mice) for chemosensitivity and response to Met inhibition with PF-2341066 (crizotinib). Human SCLC samples at diagnosis (<i>N</i> = 87) and relapse (<i>N</i> = 5) were evaluated by immunohistochemistry and immunofluorescence for EMT markers and Met status and these were correlated with patient outcome.</p><p><b>Results:</b> We identified that the activation of the Met receptor through HGF induced expression of mesenchymal markers, an aggressive phenotype, and chemoresistance. Blockade of this process with the Met inhibitor resensitized cells to chemotherapy <i>in vitro</i> and <i>in vivo</i>. Moreover, mesenchymal markers in human SCLC specimens were associated with Met activation, predicted worse survival, and were upregulated in chemorefractory disease.</p><p><b>Conclusion:</b> These results provide novel evidence on an important role of Met-dependent EMT in the adverse clinical behavior of SCLC and support clinical trials of Met inhibitors and chemotherapy in this fatal disease. <i>Clin Cancer Res; 20(4); 938–50. ©2013 AACR</i>.</p></div>" @default.
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- W4361950602 date "2023-03-31" @default.
- W4361950602 modified "2023-10-17" @default.
- W4361950602 title "Data from Targeting Epithelial-to-Mesenchymal Transition with Met Inhibitors Reverts Chemoresistance in Small Cell Lung Cancer" @default.
- W4361950602 doi "https://doi.org/10.1158/1078-0432.c.6521309.v1" @default.
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