Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells
Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells
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DOI：
10.1182/blood-2003-07-2254
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发表时间：
2004-05-01
期刊：
影响因子：
20.3
通讯作者：
Dörken, B
中科院分区：
文献类型：
--
作者：
Jundt, F;Pröbsting, KS;Dörken, B
表达在造血干细胞上的Notch受体与它们在骨髓基质细胞上的配体相互作用，从而控制细胞的命运和存活。我们最近证实Notch信号参与了经典霍奇金病B细胞来源的肿瘤细胞的增殖和生存，并描述了Notch致癌能力的新机制。在这项研究中，我们研究了Notch信号是否参与了肿瘤浆细胞与其骨髓微环境之间的紧密相互作用，这是多发性骨髓瘤(MM)肿瘤细胞生长所必需的。在这里，我们证明了Notch受体及其配体Jagged1在培养的和原代MM细胞中高度表达，而非肿瘤对应物显示低水平或检测不到Notch。功能数据表明，配体诱导的Notch信号是多发性骨髓瘤细胞的生长因子，并提示这些相互作用有助于体内的骨髓增生性疾病。(C)2004年，由美国血液病学会提供。
Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counter-parts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo. (C) 2004 by The American Society of Hematology.