Holt Randi Utne, Fagerli Unn-Merete, Baykov Vadim, Rø Torstein Baade, Hov Håkon, Waage Anders, Sundan Anders, Børset Magne
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, MTFS, N-7489 Trondheim, Norway.
Haematologica. 2008 Apr;93(4):619-22. doi: 10.3324/haematol.11867. Epub 2008 Mar 6.
Multiple myeloma is characterized by the accumulation and dissemination of malignant plasma cells in the bone marrow. Cell migration is thought to be important for these events. We studied migration in a Transwell two-chamber assay and tested the motogenic effect of various cytokines. In addition to insulin-like growth factor-1 and stromal cell-derived growth factor-1alpha, previously known as chemoattractants for myeloma cells, we identified hepatocyte growth factor as a potent attractant for myeloma cells. Hepatocyte growth factor-mediated migration was dependent on phosphatidylinositol-3-kinase, involved the MAPK/Erk signaling cascade and VLA-4 integrins, but did not involve Akt, mTOR or G proteins.
多发性骨髓瘤的特征是恶性浆细胞在骨髓中积聚和扩散。细胞迁移被认为在这些过程中起重要作用。我们在Transwell双室分析中研究了迁移,并测试了各种细胞因子的促迁移作用。除了胰岛素样生长因子-1和基质细胞衍生生长因子-1α(以前已知是骨髓瘤细胞的趋化因子)外,我们还确定肝细胞生长因子是骨髓瘤细胞的有效吸引剂。肝细胞生长因子介导的迁移依赖于磷脂酰肌醇-3激酶,涉及丝裂原活化蛋白激酶/细胞外信号调节激酶信号级联和VLA-4整合素,但不涉及Akt、mTOR或G蛋白。