Stimulation of interleukin-11 production from osteoblast-like cells by transforming growth factor-beta and tumor cell factors.
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.
Morinaga
Y
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Japan.
Fujita
N
N
Ohishi
K
K
Tsuruo
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000473:pathology*; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D017931:DNA Primers; D017370:Interleukin-11; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta