Fig. 1.

Global mda-9/syntenin knockout (mda-9^−/−) animals are innately resistant to bone metastasis. (A) A total of 3 × 10⁴ RM1-BM-Luc cells were injected by the intracardiac route (I.C.) into wild-type C57BL/6 (WT) and mda-9^−/− mice. BLI imaging was performed at day 14 to monitor bone metastasis. Representative BLI images from each experimental group are presented. Luciferase intensity was calculated using built-in Living Image Software v.2.50, and the average value for each group is graphically presented. Region of interest (ROI) was calculated and graphed based on imaging (Middle). Metastatic events in femurs were identified based on BLI imaging at a single time point, and percentage (n = 7) effects are presented (Left). (B and C) Representative ex vivo BLI photomicrographs and corresponding H/E stained sections of different organs from RM1-BM1-Luc implanted (I.C.) WT and mda-9^−/− animals. In C, the tumor is indicated by an arrow. (D) Kaplan–Meier curve showing overall survival of tumor-bearing animals from different genetic backgrounds. *P < 0.05. (E) Schematic diagram for the bone marrow transfusion protocol is described in the upper panel. Briefly, whole bone marrow cells were obtained from WT mice (BM^WT) and injected into age-matched prior irradiated (at 10 Gy) WT and mda-9^−/− mice. The “Sham Transfusion” group received bone marrow culture media only. After 8 wk, all mice were challenged with RM1-BM-Luc (I.C.). Representative ex vivo image (liver and bone) for each experimental group is presented in the lower panel. *Statistically significant (P < 0.05).