Morinaga Y, Fujita N, Ohishi K, Tsuruo T
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Japan.
Int J Cancer. 1997 May 2;71(3):422-8. doi: 10.1002/(sici)1097-0215(19970502)71:3<422::aid-ijc20>3.0.co;2-g.
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.
骨是黑色素瘤和乳腺癌细胞最常见的转移部位之一。当将人黑色素瘤（A375M）细胞和人乳腺癌（MDA-MB-231）细胞注射到BALB/c裸鼠的左心室时，这些肿瘤细胞在体内形成溶骨性骨转移。在体外新生鼠颅骨器官培养系统中，这些肿瘤细胞通过间接刺激人成骨样细胞产生骨吸收诱导因子（一种或多种）来促进骨吸收。这种分泌因子被鉴定为白细胞介素-11（IL-11）。尽管许多细胞因子和激素与成骨细胞产生IL-11有关，但发现转化生长因子-β（TGF-β）参与促进成骨细胞产生IL-11，因为添加中和性抗TGF-β抗体可降低IL-11的产生。然而，这些肿瘤细胞自身并不产生TGF-β。我们发现它们通过激活成骨样细胞产生的潜伏性TGF-β来增强IL-11的产生。我们的结果表明，转移性肿瘤细胞通过激活TGF-β诱导骨溶解，这导致成骨细胞产生IL-11以促进骨吸收。
