Nicolin Vanessa, Bortul Roberta, Bareggi Renato, Baldini Giovanna, Martinelli Bruno, Narducci Paola
Department of Biomedicine, University of Trieste, Italy.
Acta Histochem. 2008;110(5):388-96. doi: 10.1016/j.acthis.2007.12.002. Epub 2008 Apr 11.
The metastasis of breast cancer to the skeleton is a serious clinical problem resulting in hypercalcemia, bone fragility and insurmountable pain. The invasion of bony tissue by neoplastic cells usually very rapidly affects the balance between bone apposition and bone resorption. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MCF-7, were directly co-cultured with murine monocytes RAW 264.7 type CRL 2278. Compared with controls, co-culture of MCF-7 induced differentiation of multinucleated cells by membrane-bound and soluble receptor activator of NF-kB ligand (RANKL) as quantified by ELISA, Western blot analysis, transmission electron microscopy (TEM), and immunocytochemistry. The aim of this study was to determine an in vitro model system of MCF-7 human breast cancer cells grown together with monocytes to show that expression of RANKL promotes osteoclastogenesis, which may indicate a mechanism for the development of osteolytic lesions in breast cancer bone metastasis.
乳腺癌向骨骼的转移是一个严重的临床问题，会导致高钙血症、骨质脆弱和难以忍受的疼痛。肿瘤细胞对骨组织的侵袭通常会非常迅速地影响骨沉积与骨吸收之间的平衡。为了阐明癌症诱导破骨细胞生成的机制，将人乳腺癌细胞系MCF-7的细胞与小鼠单核细胞RAW 264.7（CRL 2278型）直接共培养。与对照组相比，通过ELISA、蛋白质印迹分析、透射电子显微镜（TEM）和免疫细胞化学定量分析，MCF-7共培养通过膜结合和可溶性核因子κB受体活化因子配体（RANKL）诱导多核细胞分化。本研究的目的是确定MCF-7人乳腺癌细胞与单核细胞共同生长的体外模型系统，以表明RANKL的表达促进破骨细胞生成，这可能揭示了乳腺癌骨转移中溶骨性病变发展的机制。
