Fig. 6
From: Stroma-derived miR-214 coordinates tumor dissemination
miR-214-rich Extracellular Vesicles (EVs) promote melanoma cell dissemination. A Analyses of experimental lung metastasis formation 8 days after tail vein injection of B16-F10 cells into miR-214over and miR-214ko syngeneic mice. Representative pictures of the whole lungs are shown (a, b; scale bar: 2 mm); arrows indicate metastasis formation. Relative lung metastases between the two groups of animals is presented in the graph for the indicated number (n) of mice. B CMRA-labeled B16-F10 cells (red) were pretreated for 24 h with EVs derived from miR-214over or miR-214ko CAFs and then injected into the tail vein of miR-214ko syngeneic mice for the evaluation of extravasation 2 h (a, b, c) or 48 h (d, e, f) later. Alternatively (C), extravasation was similarly evaluated for the same CMRA-labeled B16-F10 cells (red) injected into the tail vein of miR-214ko syngeneic mice in which EVs derived from miR-214over or miR-214ko CAFs were administered 24 h earlier. For (B-C) Representative fields of murine lung sections stained for CD31 (green) to highlight blood vessels and counterstained with DAPI (blue) are shown in (a, d); scale bar: 25 µm. Representative pictures of whole lungs containing red-labeled B16-F10 cells are shown in (b, c, e, f); scale bar: 1 mm; arrows indicate extravasated cells. Relative extravasated cells in the whole lungs at 48 h is shown in the graph for the indicated number (n) of mice, as mean ± SEM. D Analyses of experimental lung metastasis formation 8 days after tail vein injection of B16-F10 cells into miR-214ko syngeneic mice in which EVs derived from miR-214wt or miR-214over or miR-214.ko CAFs were systemically administered 24 h earlier. Representative pictures of the whole lungs are shown (a, b, c); scale bar: 2 mm; arrows indicate metastasis formations. Relative lung metastases between the three groups of animals are presented in the graphs for the indicated number (n) of mice. CAFs = cancer associated fibroblasts; CD31 = cluster of differentiation 31; n = number of mice; DAPI = 4’, 6-diamidino-2-fenylindole; SEM = standard error of mean. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001