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Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

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  • O E Olsen
  • K F Wader
  • K Misund
  • T K Våtsveen
  • T B Rø
  • A K Mylin
  • I Turesson
  • B F Størdal
  • S H Moen
  • T Standal
  • A Waage
  • A Sundan
  • T Holien
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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.

Original languageEnglish
JournalBlood Cancer Journal
Volume4
Pages (from-to)e196
ISSN2044-5385
DOIs
Publication statusPublished - 2014

ID: 45074470