Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells

Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. Here it is shown that BMP-4 inhibited DNA synthesis in a dose-dependent manner in 3 IL -6-dependent multiple myeloma (MM) cell lines (OH-2, IH-1, and ANBL-6), In contrast, no effect on DNA synthesis was observed in 3 IL-6-independent MM cell lines (JJN-3, U266, and RPMI 8226), BMP-4 induced cell cycle growth ar rest in the G(0)/G(1) phase in OH-2 and ANBL-6 cells but not in IH-1 cells. BMP-4 induced apoptosis in OH-2 and IH-1 cells, but not significantly in A NBL-6 cells, Furthermore, BMP-4 induced apoptosis in freshly isolated MM ce lls from 4 of 13 patients. In the OH-2 and ANBL-6 cell lines and in a patie nt sample, immunoblotting showed that BMP-4 down-regulated IL-6-induced tyr osine phosphorylation of Stat3, suggesting a mechanism for the apparent ant agonism between IL-6 and BMP-4, BMP-4 or analogues may be attractive therap eutic agents in MM because of possible beneficial effects on both tumor bur den and bone disease. (C) 2001 by The American Society of Hematology.