Fig. 8

AGR1.137 reduces tumorigenesis and metastasis in a zebrafish model. (A–D) Migration of HeLa cells treated with vehicle (DMSO) or with the selected small compounds or inhibitor as indicated, on μ-chambers in response to a CXCL12 (A, B) or CXCL2 (C, D) gradient (n=2, in duplicate, with at least 50 cells tracked in each condition). Panels (A) and (C) show representative spider plots with the trajectories of tracked cells migrating along the gradient (black) or moving in the opposite direction (red). Black and red dots in the plots represent the final position of each single tracked cell. (B, D) Quantification of the Forward Migration Index of experiments performed in (A) and (C) (mean ± SD; n=3; n.s. not significant, ****p≤0.0001). (E) Representative fluorescent images of DiI-labeled HeLa cells in zebrafish larvae treated with vehicle (DMSO), AGR1.131 50 μM, AGR1.137 50 μM or AMD3100 10 μM at 0 or 3 days post-implantation and treatment. Quantitation of the relative tumor size at day 3 compared with that of day 0 normalized to the relative tumor size in the DMSO control group, is shown for each experimental group (mean ± SD; n=20; n.s. not significant, **p≤0.01). (F) Representative fluorescent images of the caudal hematopoietic plexus of larvae from the same groups as shown in E at 3 days postimplantation. Quantitation of the relative amount of metastasized cells in each group relative to DMSO-controls is shown (mean ± SD; n=20, n.s. not significant, * p≤0.05, *** p≤0.001).