MM-derived autocrine and exogenous SHH promote MM cell proliferation and survival. Proliferation of (A) ARP-1 or CAG cells in culture media in the presence or absence of cyclopamine or aSHH. (B) Proliferation of ^vecARP-1/CAG, ^SHH+ARP-1/CAG, or ^SHH–ARP-1/CAG cells in culture media. Cell proliferation was assayed daily for 5 consecutive days. (C) Proliferation of ARP-1, CAG, RPMI-8226, and U266 cells in culture media with the addition of different concentrations (0 to 1.0 μg/mL) of rhSHH. (D) Percentages of apoptotic CD138⁺ primary MM cells purified from BM aspirates of 6 patients with MM (Pt MM) in a 24-hour culture with or without the addition of aSHH or control IgG (ctl IgG) (5 μg/mL) or rhSHH (5 ng/mL). (E) Percentages of apoptotic wild-type ARP-1 or CAG cells in a 3-day culture with or without the addition of cyclopamine (10 μM) or aSHH or control IgG (5 μg/mL). (F) Percentages of apoptotic ^vecARP-1/CAG, ^SHH+ARP-1/CAG, or ^SHH–ARP-1/CAG cells in a 3-day culture with or without the addition of cyclopamine (10 μM) or aSHH or control IgG (5 μg/mL). Cell apoptosis was detected by Annexin-V binding assay. *P < .05; **P < .01.