RANKL-dependent and RANKL-independent mechanisms of macrophage-osteoclast differentiation in breast cancer.

摘要: The cellular and humoral mechanisms accounting for tumour osteolysis in metastatic breast cancer are uncertain. Osteoclasts, the specialised multinucleated cells responsible osteolysis, derived from monocyte/macrophage precursors. Breast cancer-derived tumour-associated macrophages (TAMs) capable of osteoclast differentiation but controlling this activity In study, TAMs were isolated primary cancers cultured presence absence cytokines/growth factors influencing osteoclastogenesis. Extensive TAM-osteoclast occurred only RANKL M-CSF; process was inhibited by OPG RANK:Fc, decoy receptors RANKL. fibroblasts human bone stromal expressed mRNA RANKL, TRAIL, co-culture these with monocytes stimulated formation a RANKL-dependent mechanism. Osteoclast lacunar resorption also RANKL-independent mechanism when conditioned medium cells, MDA-MB-231 MCF-7, added (with M-CSF) to monocyte cultures. Our findings indicate that contribute producing soluble influence respectively.