Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors
Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors
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DOI：
10.1038/sj.leu.2404226
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发表时间：
2006-06-01
期刊：
影响因子：
11.4
通讯作者：
Pellat-Deceunynck, C
中科院分区：
文献类型：
--
作者：
Jego, G;Bataille, R;Pellat-Deceunynck, C
多发性骨髓瘤（MM）患者非常容易感染，这仍然是死亡的主要原因。在感染期间，人类免疫细胞通过Toll样受体家族（TLR）感知入侵病原体的存在，TLR识别病原体相关分子模式（PAMP）。我们假设MM细胞也可以感知微生物的存在，从而促进骨髓瘤疾病的进展。在这里，我们报告，人类骨髓瘤细胞系（HMCL）和原代骨髓瘤细胞表达广泛的TLR，并对相应的PAMP敏感。Toll样受体1、7和9最常由HMCL表达。TLR的表达模式与B细胞的表达模式不相关，因为TLR 2和10被丢失，而TLR 3、4和8被一些HMCL获得。用TLR 7-和TLR 9-配体培养使HMCL免于血清剥夺或地塞米松诱导的细胞凋亡。类似地，两种配体都增加骨髓瘤细胞生长。这些作用是由白细胞介素-6（IL-6）的自分泌介导的，因为IL-6的中和阻断了HMCL的生长和存活。因此，TLR的表达和功能不限于免疫系统的细胞，并且可能对癌细胞有利。在MM中，复发性感染可促进肿瘤生长并有利于逃避标准治疗。
Multiple myeloma (MM) patients are strongly vulnerable to infections, which remain a major cause of death. During infection, human immune cells sense the presence of invading pathogens through the Toll-like receptor family (TLR), which recognizes pathogen-associated molecular patterns (PAMP). We hypothesized that MM cells also could sense the presence of microorganisms, thus promoting myeloma disease progression. Here, we report that human myeloma cell lines (HMCL) and primary myeloma cells express a broad range of TLR, and are sensitive to the corresponding PAMP. Toll-like receptor 1, 7 and 9 are most frequently expressed by HMCL. The expression pattern of TLR does not correlate with the one of B cells, as TLR2 and 10 are lost while TLR3, 4 and 8 are acquired by some HMCL. Culture with TLR7- and TLR9-ligands saves HMCL from serum-deprivation or dexamethasone-induced apoptosis. Similarly, both ligands increase myeloma cell growth. These effects are mediated by an autocrine secretion of interleukin-6 (IL-6) since the neutralization of IL-6 blocks the growth and survival of HMCL. Thus, TLR expression and function are not restricted to the cells of the immune system and could be of advantage for cancer cells. In MM, recurrent infections could promote tumor growth and favor escape from standard therapies.