Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / secondary
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Animals
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Apoptosis Regulatory Proteins
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Colonic Neoplasms / pathology
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Enzyme Activation
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Inflammation / chemically induced
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Inflammation / pathology*
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Lipopolysaccharides
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Lung Neoplasms / enzymology*
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Lung Neoplasms / pathology
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Lung Neoplasms / secondary
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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NF-kappa B / physiology*
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Neoplasm Transplantation
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Apoptosis Regulatory Proteins
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Lipopolysaccharides
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Membrane Glycoproteins
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NF-kappa B
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TNF-Related Apoptosis-Inducing Ligand
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha