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. 2017 Oct 31;11(12):1788–1805. doi: 10.1002/1878-0261.12145

Figure 7.

Figure 7

Dasatinib inhibits cell proliferation, local dissemination, and metastatic dissemination in vivo. (A) Analysis of NRG, MMP13, pERK1/2, and ERK1/2 in MCF7 and MCF7‐NRGα2c‐Luc cells pretreated or not with dasatinib for 24 h by western blotting. The asterisk indicates the heavy chain band of the antibody used for MMP13 immunoprecipitation. Levels of GAPDH were used as a loading control. (B) Bioluminescence whole‐body images of mice injected with MCF7‐NRGα2c‐Luc cells and treated with dasatinib or not (vehicle control). Images were taken 90 days after injection. The rainbow‐colored bar at the right of the images represents the intensity scale of the luminescence signal. The arrows point to the disseminated tumoral masses. The table at the bottom shows the number of mice with metastasis in each experimental group at 60, 75, and 90 days after injection (n = 5 mice per experimental condition). (C) Graphic representation of primary tumor growth analyzed weekly by measuring photon flux with an IVIS 50 Imaging system after the beginning of the treatment in each group. The treatment began 30 days after injection. Data are presented as the mean ± SD of the primary tumors assayed in each experimental condition. Comparisons of means between two independent groups were made using a two‐sided Student's t‐test. (D) Column scatter graph showing the local dissemination of the primary tumors in each group as indicated by measurements of the width of the luminescent signals 90 days after injection. Horizontal bars in each plot indicate the location of the mean. Data are presented as the mean ± SD of the primary tumors of each group. Comparisons of means between two independent groups were made using a two‐sided Student's t‐test. (E) Western blotting analysis of MMP13, pSFK, and pERK1/2 in primary tumor samples from MCF7‐NRGα2c‐Luc cell‐injected mice treated with dasatinib (tumors 3 and 4) or not (tumors 1 and 2) 90 days after injection. NRG‐stimulated MCF7 cell extracts were used as a control of detection of the above‐mentioned proteins. Levels of ERK1/2 were used as a loading control. (F) Schematic representation of the effect of NRG on MMP13 upregulation and breast cancer metastasis, as well as the expected effect of dasatinib on this process. The letter D refers to dasatinib. Data information: In (A), results from a representative experiment that was repeated twice are shown.