KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
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.
Blood Cancer J. 2014 Mar 21;4(3):e196. doi: 10.1038/bcj.2014.16.
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.
多发性骨髓瘤是一种主要位于骨髓中的浆细胞恶性肿瘤。许多骨形态发生蛋白（BMPs）在体外诱导骨髓瘤细胞凋亡，本研究将 BMP-9 添加到该列表中。在体外，已在人血清中发现浓度可抑制癌细胞生长的 BMP-9。我们在此表明，与健康对照者（中位数 110pg/ml，范围 8-359）相比，骨髓瘤患者血清中的 BMP-9 水平升高（中位数 176pg/ml，范围 8-809）。BMP-9 也存在于骨髓中，并通过 ALK2 信号通路能够诱导 11 个原发性骨髓瘤细胞样本中的 4 个发生凋亡。BMP-9 诱导骨髓瘤细胞凋亡与 c-MYC 下调有关。BMP-9 的作用被骨髓微环境中存在的膜结合（CD105）或可溶性内皮素抵消，这表明了骨髓瘤细胞如何逃避 BMP-9 在多发性骨髓瘤中的肿瘤抑制活性的机制。
