Toll-like receptor 4 signaling promotes tumor growth

Che Hsin Lee, Chao Liang Wu, Ai Li Shiau

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)


Chronic inflammation is a potential risk factor for tumor progression. The molecular mechanisms linking chronic inflammation and tumor growth have proven elusive. Herein, we describe a new role for Toll-like receptor 4 (TLR4) in tumor-associated macrophages (TAMs) in promoting tumor growth. TAMs can remodel tumor microenvironment and promote tumor growth. With the use of mice lacking TLR4 signaling, we show that TLR4 signaling influences tumor growth and that TLR4 signaling is a critical upstream activator of nuclear factor-kappa B (NF-κB) in TAMs. TLR4-deficient TAMs produce neither proinflammatory cytokines nor angiogenic factors, and activate no NF-κB activity in tumor cells. Furthermore, using macrophage/tumor cell coculture system and adoptive transfer of macrophages with functional TLR4 macrophages to TLR4-deficient mice bearing tumors, we demonstrate an essential role for TLR4 signaling in inducing NF-κB activity in tumor cells and enhancing tumor growth. Antibody neutralization experiments reveal that TAMs are stimulated by heat shock proteins derived from tumor cells through TLR4, leading to production of growth factors, which may in turn promote tumor growth via NF-κB signal pathway. Therefore, this signaling cascade may represent a therapeutic target in cancer.

頁(從 - 到)73-82
期刊Journal of Immunotherapy
出版狀態Published - 2010 1月 1

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 免疫學
  • 藥理
  • 癌症研究


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