MM-derived autocrine SHH promotes MM cell growth and drug resistance in vivo. Shown are tumor burdens detected as (A) tumor volumes or (B) levels of M-protein secreted by human MM cells (^vecARP-1, ^SHH+ARP-1, or ^SHH–ARP-1 cells) in SCID mice, and (C) survival of the mice. In this experiment, 2 × 10⁶ MM cells were injected into SCID mice subcutaneously. Tumor volume (in cubic millimeters) was measured every 3 days, and the levels of circulating M-protein were detected weekly by ELISA. Also shown are (D) tumor volumes and (E) survival of ARP-1–inoculated mice treated with Mel in combination with aSHH. Injection of PBS, control IgG, aSHH, or Mel alone served as controls. In these experiments, when subcutaneous tumors reached 5 mm in diameter, mice were treated with intraperitoneal injections of Mel (50 μg per mouse every 3 days for the duration of the experiment) or 50 μL PBS, with or without aSHH or control IgG (5 μg per mouse every 3 days for the duration of the experiment) injected around the tumor. Mice were euthanized when they became moribund or when subcutaneous tumors reached 15 mm in diameter. (F) Levels of M-protein secreted by ^vecARP-1– or ^SHH–ARP-1–inoculated SCID-hu mice treated with Mel in combination with aSHH. Injection of PBS, control IgG, aSHH, or Mel alone served as controls. *P < .05; **P < .01.