Toll-like receptors mediate proliferation and survival of multiple myeloma cells
Toll-like receptors mediate proliferation and survival of multiple myeloma cells
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DOI：
10.1038/sj.leu.2404225
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发表时间：
2006-06-01
期刊：
影响因子：
11.4
通讯作者：
Sundan, A
中科院分区：
文献类型：
--
作者：
Bohnhorst, J;Rasmussen, T;Sundan, A
多发性骨髓瘤（MM）是一种无法治愈的B细胞恶性肿瘤，其特征在于（a）恶性浆细胞在骨髓（BM）中累积和复发或持续感染。Toll样受体（TLR）在宿主防御感染中是必不可少的，目前已经鉴定了10种人TLR（TLR 1-TLR 10）和一种TLR同源物（RP 105）。B细胞表达多种TLR（主要是TLR 1、6、7、9、10和RP 105），并且在B细胞中TLR启动的反应包括增殖、抗凋亡作用和浆细胞（PC）分化。本研究旨在分析类铎受体在多发性骨髓瘤中的作用。我们发现，多发性骨髓瘤患者的细胞系中检测到类铎受体的频繁表达（每个细胞系中至少有6个类铎受体）。相比之下，只有少数TLR（主要是TLR 1和/或RP 105）被发现在来自健康供体BM的PC中表达。此外，TLR特异性配体诱导MM细胞系增殖和存活增加，部分原因是自分泌白细胞介素-6产生。重要的是，我们证明了MM患者的PC也会对TLR特异性配体产生增殖反应。总之，TLR配体可能有助于MM患者MM细胞的生长和存活。
Multiple myeloma (MM) is an incurable B-cell malignancy characterized by (a)ccumulation of malignant plasma cells in bone marrow (BM) and recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections and today 10 human TLRs (TLR1-TLR10) and one TLR-homolog (RP105) have been characterized. B cells express several TLRs (mainly TLR1, 6, 7, 9, 10 and RP105) and TLR-initiated responses in B cells include proliferation, antiapoptosis effect and plasma cell (PC) differentiation. The present study was designed to analyze the role of TLRs in MM. We show that frequent expressions of TLRs were detected in cell lines from MM patients (minimum six TLRs in each). In comparison, only few TLRs (mainly TLR1 and or RP105) were found expressed in PCs from BM of healthy donors. In addition, TLR-specific ligands induce increased proliferation and survival of the MM cell lines, partially due to an autocrine interleukin-6 production. Importantly, we demonstrate that also PC from MM patients proliferates in response to TLR-specific ligands. In conclusion, TLR-ligands may contribute to increased growth and survival of MM cells in MM patients.