Chikatsu N, Takeuchi Y, Tamura Y, Fukumoto S, Yano K, Tsuda E, Ogata E, Fujita T
Division of Endocrinology, University of Tokyo School of Medicine, Tokyo, 112-8688, Japan.
Biochem Biophys Res Commun. 2000 Jan 19;267(2):632-7. doi: 10.1006/bbrc.1999.2008.
Cancer cells metastasized to bone induce osteoclastogenesis for bone destruction. Coculture of either mouse melanoma B16 or breast cancer Balb/c-MC cells with mouse bone marrow cells (BMCs) induced osteoclast-like cells, which were not observed when cancer cells were segregated from BMCs. Osteoclast differentiation factor (ODF), also known as receptor activator of NF-kappaB ligand (RANKL), is a direct mediator of many osteotropic factors. Neither BMCs, B16 nor Balb/c-MC cells alone expressed ODF mRNA. However, coculture of these cancer cells with BMCs induced ODF expression, which was prevented by indomethacin. Moreover, the coculture with cancer cells inhibited secretion of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF), an inhibitory decoy receptor for ODF, from BMCs. Thus, enhanced osteoclastogenesis in the presence of cancer cells might be due to an increase in ODF activity. These results suggest that interactions between cancer cells and BMCs induce ODF expression and suppress OPG/OCIF level in metastatic foci resulting in pathological osteoclastogenesis for bone destruction.
转移至骨的癌细胞诱导破骨细胞生成以破坏骨骼。将小鼠黑色素瘤B16细胞或乳腺癌Balb/c-MC细胞与小鼠骨髓细胞（BMC）共培养可诱导破骨细胞样细胞的生成，而当癌细胞与BMC分离时则未观察到这种情况。破骨细胞分化因子（ODF），也称为核因子κB受体活化因子配体（RANKL），是许多促骨因子的直接介质。单独的BMC、B16细胞或Balb/c-MC细胞均不表达ODF mRNA。然而，这些癌细胞与BMC共培养可诱导ODF表达，吲哚美辛可抑制这种表达。此外，与癌细胞共培养可抑制BMC分泌骨保护素/破骨细胞生成抑制因子（OPG/OCIF），这是一种ODF的抑制性诱饵受体。因此，在癌细胞存在的情况下破骨细胞生成增强可能是由于ODF活性增加所致。这些结果表明，癌细胞与BMC之间的相互作用诱导转移灶中ODF表达并抑制OPG/OCIF水平，从而导致病理性破骨细胞生成以破坏骨骼。
