Overproduction of IL-8 results in suppression of bone metastasis by lung cancer cells in vivo.

HARA-B cells were established from the bone lesion in nude mice formed after an intracardiac inoculation of the human lung cancer-derived cells (HARA), and production of IL-8 in HARA-B cells was decreased as compared to that in the parental HARA cells. This suggests a possible relationship between IL-8 production and bone metastasis. Thus, we examined the effect of IL-8 on bone metastasis using HARA-B cells transfected with experimental (IL-8-cDNA) and/or control plasmid in the experimental bone metastasis model in nude mice. Growth rates of both cells in vitro were similar. Control cells developed radiologically detectable bone metastases in 50% of nude mice tested, whereas experimental cells did not develop bone metastases. Osteoclastic bone resorption is an important step in the process of bone metastasis, and IL-8 possesses an inhibitory effect on osteoclastic bone resorption. These results suggest that IL-8 suppresses bone metastasis, which might be attributed to the inhibitory effect of IL-8 on osteoclastic bone resorption.