Stimulation of interleukin-11 production from osteoblast-like cells by transforming growth factor-β and tumor cell factors

✍ Scribed by Yoshihiro Morinaga; Naoya Fujita; Kazuo Ohishi; Takashi Tsuruo

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 158 KB
• Volume: 71
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970502)71:3<422::aid-ijc20>3.0.co;2-g

✦ Synopsis

Bone is one of the most common sites of metastasis in melanoma and breast cancer cells. Human melanoma (A375M) and human breast cancer (MDA-MB-231) cells form osteolytic bone metastasis in vivo when these tumor cells are injected into the left ventricles of BALB/c nude mice. These tumor cells promote bone resorption in the in vitro neonatal murine calvaria organ culture system by indirectly stimulating the production of a bone resorption-inducing factor (or factors) from human osteoblast-like cells. This secreted factor was identified as interleukin-11 (IL-11). Although many cytokines and hormones were associated with IL-11 production from osteoblasts, transforming growth factor-beta (TGF-beta) was found to be involved in the promotion of IL-11 production from osteoblasts, because the addition of a neutralizing anti-TGF-beta antibody decreased the production of IL-11. However, these tumor cells did not produce TGF-beta by themselves. We found that they enhanced IL-11 production by activating latent TGF-beta produced from osteoblast-like cells. Our results indicate that metastatic tumor cells induce osteolysis by activating TGF-beta, which leads IL-11 production from osteoblasts to promote bone resorption.