Fig. 6.

The CXCR4 antagonist IT1t reduces metastatic tumor burden in vivo. IT1t (20 µM) was applied into the cell medium for 24 h prior to engraftment in zebrafish embryos to antagonize CXCR4 receptor activation (A). The percentage of live cells after treatment was not significantly different than in the control condition (three independent experiments) (B). The metabolic activity, readout of cell growth, was not significantly affected when increasing concentrations of IT1t were used (C). Pre-treatment in vitro caused a reduction in tumor burden at the secondary site in vivo, both at 2 dpi (D) and 4 dpi (E). Cancer cell burden increased over time from 2 to 4 dpi in the control group, whereas it remained at comparable levels upon treatment (F). Data set in F is obtained by using the same data points as shown in D and E. Number of larvae is n=64 (DMSO) and n=75 (IT1t) at 2 dpi and n=59 (DMSO) and n=56 (IT1t) at 4 dpi. (G) Effect of CXCR4 inhibition on tumor burden over time is shown. Scale bars: 50 µm. Data are mean±s.e.m. from two independent experiments. Statistical analysis: two-tailed, unpaired t-test and ANOVA with Bonferroni post-hoc test for datasets with two or more groups respectively. ****P<0.0001; **P=0.005; ns, P>0.05.