The biological sequelae of stromal cell-derived factor-1alpha in multiple myeloma.
The biological sequelae of stromal cell-derived factor-1alpha in multiple myeloma.
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发表时间：
2002
影响因子：
5.7
通讯作者：
T. Hideshima;D. Chauhan;Toshiaki Hayashi;K. Podar;M. Akiyama;Deepak K. Gupta;P. Richardson;N. Munshi;K. Anderson
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文献类型：
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作者：
T. Hideshima;D. Chauhan;Toshiaki Hayashi;K. Podar;M. Akiyama;Deepak K. Gupta;P. Richardson;N. Munshi;K. Anderson
基质细胞衍生因子（SDF）-1 α介导正常造血干细胞的迁移，但其在恶性血液病中的作用尚不明确。在这项研究中，我们检测了10名MM患者（多发性骨髓瘤; 2.6 +/- 1.5 ng/ml）的骨髓（BM）血浆和5名MM患者（0.6 +/- 0.2 ng/ml）的BM基质细胞培养上清液中的SDF-1 α。我们发现SDF-1 α促进MM细胞增殖，诱导迁移，并保护MM细胞免受地塞米松诱导的凋亡，但这些作用仅是适度的。在MM细胞系和患者MM细胞中，SDF-1 α诱导p42/44丝裂原活化蛋白激酶以及Akt及其下游靶点Bad的磷酸化，并激活核因子-κ B。在BM环境中，SDF-1 α上调BM基质细胞中白细胞介素6和血管内皮生长因子的分泌，促进肿瘤细胞生长、存活和迁移。这些数据表明，SDF-1 α促进骨髓微环境中MM细胞的生长、迁移和耐药性，但这些作用仅是适度的，因此SDF-1 α并不代表这种疾病的新疗法的靶点。
Stromal cell-derived factor (SDF)-1alpha mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1alpha in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 +/- 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 +/- 0.2 ng/ml). We show that SDF-1alpha promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1alpha induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-kappaB. In the BM milieu, SDF-1alpha up-regulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1alpha promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1alpha therefore does not represent a target for novel therapeutics in this disease.