Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression

Cancer Cell. 2004 Sep;6(3):297-305. doi: 10.1016/j.ccr.2004.08.012.


We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / secondary
  • Animals
  • Apoptosis Regulatory Proteins
  • Colonic Neoplasms / pathology
  • Enzyme Activation
  • Inflammation / chemically induced
  • Inflammation / pathology*
  • Lipopolysaccharides
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / physiology*
  • Neoplasm Transplantation
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / physiology*


  • Apoptosis Regulatory Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • NF-kappa B
  • TNF-Related Apoptosis-Inducing Ligand
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha