Olsen, O E1; Wader, K F3; Misund, K3; Våtsveen, T K3; Rø, T B3; Mylin, A K2; Turesson, I3; Størdal, B F3; Moen, S H3; Standal, T3; Waage, A3; Sundan, A3; Holien, T3
1 The research unit for general practice, The Capital Region of Denmark2 Hæmatologisk Klinik, Finsencentret, Rigshospitalet, The Capital Region of Denmark3 unknown
Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8-809) compared with healthy controls (median 110 pg/ml, range 8-359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma.