|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1998 : ¥2,200,000 (Direct Cost : ¥2,200,000)
BACKGROUND. Osteoclastic bone resorption is an important step in bone invasion in several malignancies. Although IL-6 accelerates osteoclastic bone resorption, it remains unclear whether IL-6 may be involved in bone invasion of oral cancer.
METHODS. The pit-formation assay with calf femur-derived bone slices was performed to examine the bone-resorbing activity of osteoclasts and cancer cells. The chemotaxis activity of the culture media were analyzed by the use of Boyden chamber technique. Nude mice which were inoculated IL-6-producing oral cancer cells into masseter, were treated with anti-IL-6 neutralizing antibody, and mandibular bone invasion of the cells were assessed.
RESULTS. BHY, a bone invasive oral cancer cell line, but not HNT, a non-invasive cell line, produced large amounts of IL-6. In a pit-formation asssay, addition of conditioned medium (CM) derived from BHY but not HNT increased osteoclastic bone resorption and the effects were inhibited by anti-IL-6 antibody. BHY-secreted IL-6 showed significant chemotaxis activity for osteoclasts. Interestingly, CM from the cocultivation of osteoclasts and BHY markedly enhanced the cancer cell migration, and the chemotaxis activity were significantly reduced when anti-IL-6 antibody was added into the coculture then CM were collected, but not when the antibody was added into the CM after they were collected. Futhermore, treatment with anti-IL-6 antibody almost completely inhibited mandibular bone invasion of BHY in nude mice.
CONCLUSIONS. These results strongly suggest that IL-6 secreted by oral cancer cells plays a significant role in bone invasion.