title: Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.
abstract: 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.
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: O E
authors.initials: OE
authors.lastname: Olsen
authors.affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Oncology, St Olav's University Hospital, Trondheim, Norway.
authors.forename: K F
authors.initials: KF
authors.lastname: Wader
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Misund
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T K
authors.initials: TK
authors.lastname: Våtsveen
authors.affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Pediatrics, St Olav's University Hospital, Trondheim, Norway.
authors.forename: T B
authors.initials: TB
authors.lastname: Rø
authors.affiliation: Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A K
authors.initials: AK
authors.lastname: Mylin
authors.affiliation: Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Turesson
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: B F
authors.initials: BF
authors.lastname: Størdal
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: S H
authors.initials: SH
authors.lastname: Moen
authors.affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] CEMIR (Centre of Molecular Inflammation Research), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Standal
authors.affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Hematology, St Olav's University Hospital, Trondheim, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Waage
authors.affiliation: 1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] CEMIR (Centre of Molecular Inflammation Research), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Sundan
authors.affiliation: KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Holien