Figure 7 from A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer

Dependency on Lgr5+ CSCs in RMC-9945–treated metastases. A, Relative mRNA expression of Gfp and Lgr5 genes in sorted GFP-high, -medium, -low, and -negative population from AKTP MTO-derived liver metastases. Mean ± SEM. B, Schematics of in vivo RMC-9945 treatment (7 days, starting at day 21 after implantation), Diphtheria toxin (DT) treatment (one injection any other day), or combination of RMC-9945 and DT, of liver metastases implanted in the spleen of C57BL/6J mice. C, Representative histograms of Lgr5-EGFP expression of the EPCAM+/CD45− population in mice treated with vehicle, RMC-9945, DT, and RMC-9945 + DT obtained by flow cytometry. D, Representative pictures of livers after 7 days of treatment with vehicle, RMC-9945, DT, and RMC-9945 + DT. Arrows pointing at liver metastases. E and F, Quantifications of total number of metastases per mouse in each condition described (E) and of the proportion of metastases per size (higher diameter; F). Vehicle n = 5 mice, RMC-9945 n = 10, DT n = 8, and RMC-9945 + DT = 7. Mean ± SEM. For E, P values are derived from ANOVA followed by Tukey tests. For F, P values are derived from the β-binomial regression model. G, Schematics of in vivo RMC-9945 treatment (10 days, starting at day 15 after implantation), DT treatment (one injection every day), or combination of RMC-9945 and DT, of liver metastases implanted in the spleen of C57BL/6J mice. H and I, Quantifications of total number of metastases per mouse in each condition described (H) and of the proportion of metastases per size (higher diameter; I). Vehicle n = 8 mice, RMC-9945 n = 12, DT n = 8, and RMC-9945 + DT = 12. Mean ± SEM. For H, P values are derived from ANOVA followed by Dunnett tests. For I, P values are derived from the β-binomial regression model. J, Representative pictures of livers after 10 days of treatment with vehicle, RMC-9945, DT, and RMC-9945 + DT. Arrows pointing at liver metastases. K, Kaplan–Meier survival plot of mice treated with the indicated treatments. P values are derived from Gehan–Breslow–Wilcoxon test.