Jundt Franziska, Pröbsting Kristina Schulze, Anagnostopoulos Ioannis, Muehlinghaus Gwendolin, Chatterjee Manik, Mathas Stephan, Bargou Ralf C, Manz Rudolf, Stein Harald, Dörken Bernd
Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany.
Blood. 2004 May 1;103(9):3511-5. doi: 10.1182/blood-2003-07-2254. Epub 2004 Jan 15.
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 counterparts 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.
造血干细胞上表达的Notch受体与骨髓基质细胞上的配体相互作用，从而控制细胞命运决定和存活。我们最近证明，Notch信号通路参与经典霍奇金病B细胞来源肿瘤细胞的增殖和存活，并描述了Notch致癌能力的一种新机制。在本研究中，我们调查了Notch信号通路是否参与肿瘤性浆细胞与其骨髓微环境之间的紧密相互作用，而这种相互作用对多发性骨髓瘤（MM）中肿瘤细胞的生长至关重要。在此我们证明，Notch受体及其配体Jagged1在培养的和原发性MM细胞中高度表达，而非肿瘤性对应细胞显示出低水平至无法检测到的Notch。功能数据表明，配体诱导的Notch信号通路是MM细胞的生长因子，并提示这些相互作用有助于体内骨髓瘤的发生。
