Both Host and Tumor Involved in Metastasis

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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