Human lung cancer cells express functionally active Toll-like receptor 9.
Human lung cancer cells express functionally active Toll-like receptor 9.
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DOI：
10.1186/1465-9921-6-1
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发表时间：
2005-01-04
影响因子：
5.8
通讯作者：
Goldmann T
中科院分区：
文献类型：
--
作者：
Droemann D;Albrecht D;Gerdes J;Ulmer AJ;Branscheid D;Vollmer E;Dalhoff K;Zabel P;Goldmann T
CpG 寡核苷酸 (CpG-ODN) 通过 Toll 样受体 9 (TLR9) 诱导信号传导，目前正在研究作为感染和癌症治疗的佐剂。 CpG-ODN 作为 Th-1 佐剂发挥作用，能够激活树突状细胞。在人类中，TLR9 据描述在 B 淋巴细胞、单核细胞、浆细胞样树突细胞中强烈表达，而在人类呼吸细胞中表达水平较低。我们确定了细菌 DNA 与肿瘤细胞本身是否可能直接相互作用，并研究了 TLR9 在人类恶性实体瘤和细胞系中的表达和功能。恶性肿瘤细胞表达的 TLR9 一方面会影响使用 CpG-ODN 的治疗方法，另一方面提供有关肿瘤细胞在肿瘤免疫学中的作用的额外新信息。使用免疫组织化学、共聚焦显微镜、原位杂交、RT-PCR 和 DNA 测序评估 HOPE 固定的非小肺癌、非恶性组织和肿瘤细胞系中 TLR9 的表达。通过FACS分析和Bio-Plex系统检测细胞凋亡和趋化因子表达。我们发现大多数肺癌标本以及所有测试的肿瘤细胞系中肿瘤细胞的细胞质中存在高 TLR9 信号强度。与此相反，非恶性肺组织仅表现出零星的弱表达。用 CpG-ODN 刺激 HeLa 和 A549 细胞诱导单核细胞趋化蛋白-1 的分泌，并减少自发性和肿瘤坏死因子-α 诱导的细胞凋亡。在这里，我们展示了 TLR9 在精选的人类肺癌组织和各种肿瘤细胞系中表达。人类恶性肿瘤中功能活跃的 TLR9 表达可能会影响使用 CpG-ODN 的治疗方法，并表明恶性细胞可以被视为肿瘤免疫学中的活跃参与者。
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology. The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system. We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis. Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.
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影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
2.8
作者：
Goldmann, T;Wiedorn, KH;Vollmer, E
通讯作者：
Vollmer, E
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4.4
作者：
Park, Y;Lee, SW;Sung, YC
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Sung, YC
影响因子：
56.9
作者：
Aliprantis, AO;Yang, RB;Zychlinsky, A
通讯作者：
Zychlinsky, A
影响因子：
2.6
作者：
Decker, T;Schneller, F;Peschel, C
通讯作者：
Peschel, C