Both Host and Tumor Involved in Metastasis

Cancer researchers studying how tumor cells metastasize and spread to other areas of the body have found that the process requires biochemical factors produced by both the host and the tumor.

Investigators at the University of California, San Diego (La Jolla, USA) worked with an experimental mouse cancer metastasis model in which a colon adenocarcinoma cell line spreads to the lungs in response to stimulation by an injection of bacterial lipopolysaccharide (LPS).

They reported in the September 20, 2004, issue of Cancer Cell that LPS-induced metastatic growth response in this model depended on both tumor necrosis factor alpha (TNF-alpha) production by host hematopoietic cells and nuclear factor-kappa B (NF-kappa B) activation in tumor cells.


In experiments where production of NF-kappa B was inhibited in both colon and mammary carcinoma cells, the LPS-induced growth response changed to LPS-induced tumor regression. This response was TNF-alpha-independent, but depended on another member of the TNF superfamily, TRAIL (TNF-related apoptosis-inducing ligand), whose receptor is induced in NF-kappa B-deficient cancer cells.

First author Dr. Jun-Li Luo, a researcher in the laboratory of gene regulation and signal transduction at the University of California, San Diego, explained, "Normally, inflammation associated with malignancy activates NF-kappa B, TNF-alpha and TRAIL, all at the same time. However, NF-kappa B has the upper hand, and with TNF-alpha, stimulates tumor growth faster than TRAIL can inhibit it. Our results suggest that it is possible to use NF-kappa B or TNF-alpha inhibitors to prevent inflammation-induced tumor growth, thus destroying their advantage, and allowing TRAIL to tip the balance in its favor.”




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