https://scholars.lib.ntu.edu.tw/handle/123456789/550472
標題: | Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis | 作者: | Kim S. Takahashi H. WAN-WAN LIN Descargues P. Grivennikov S. Kim Y. Luo J.-L. Karin M. |
公開日期: | 2009 | 卷: | 457 | 期: | 7225 | 起(迄)頁: | 102-106 | 來源出版物: | Nature | 摘要: | Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-α (TNF-α) through activation of the Toll-like receptor (TLR) family members TLR2 and TLR6. Both TNF-α and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC-conditioned medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer, as a macrophage activator that acts through TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-α secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth. ?2009 Macmillan Publishers Limited. All rights reserved. |
URI: | 2-s2.0-58149269348 https://scholars.lib.ntu.edu.tw/handle/123456789/550472 |
ISSN: | 280836 | DOI: | 10.1038/nature07623 | SDG/關鍵字: | CD14 antigen; interleukin 6; proteoglycan; toll like receptor 2; toll like receptor 6; tumor necrosis factor alpha; cancer; cytology; immune system; tumor; animal cell; animal experiment; animal model; article; biochemistry; bone marrow cell; cancer cell culture; carcinoma; controlled study; cytokine production; extracellular matrix; innate immunity; Lewis carcinoma; lung cancer; macrophage activation; metastasis; mouse; nonhuman; priority journal; protein purification; upregulation |
顯示於: | 藥理學科所 |
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