Cellular mechanisms of bone resorption in breast carcinoma

Cellular mechanisms of bone resorption in breast carcinoma
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乳腺癌骨吸收的细胞机制

DOI:
--
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发表时间:
2001
影响因子:
8.8
通讯作者:
N. Athanasou
N. Athanasou
中科院分区:
医学1区
文献类型:
--
作者:
N. Hunt;Y. Fujikawa;A. Sabokbar;I. Itonaga;A. Harris;N. Athanasou

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导致骨性乳腺癌转移中破骨细胞数量增加和骨吸收的细胞机制尚不清楚。破骨细胞是骨髓来源的细胞,由在单核细胞部分中循环的单核吞噬细胞前体融合形成。在这项研究中,我们确定了与原发性乳腺癌患者和年龄匹配的正常对照相比,骨转移乳腺癌患者(±高钙血症)的循环破骨细胞前体数量是否增加,或者对破骨细胞生成的体液因子的敏感性是否增加。在盖玻片和牙本质切片上存在 1,25 二羟基维生素 D3 [1,25(OH)2D3] 和人巨噬细胞集落刺激因子 (M-CSF) 的情况下,分离单核细胞并与 UMR 106 成骨细胞共培养。有限稀释实验表明,与对照组相比,患有骨转移的乳腺癌患者(±高钙血症)循环破骨细胞前体细胞的数量没有增加。这些患者的破骨细胞前体在破骨细胞形成方面也没有表现出对 1,25(OH)2D3 或 M-CSF 的敏感性增加。添加甲状旁腺激素相关蛋白和白细胞介素6并没有增加破骨细胞的形成。然而,添加培养的乳腺癌细胞系(MCF-7和MDA-MB-435)的上清液,以剂量依赖性方式显着增加单核细胞破骨细胞的形成。这些结果表明乳腺癌中破骨细胞形成的增加并不是由于循环破骨细胞前体的数量/性质的增加。他们还表明肿瘤细胞通过分泌可溶性破骨细胞因子促进骨微环境中破骨细胞的形成。 © 2001 癌症研究运动 http://www.bjcancer.com
The cellular mechanisms that account for the increase in osteoclast numbers and bone resorption in skeletal breast cancer metastasis are unclear. Osteoclasts are marrow-derived cells which form by fusion of mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have determined whether circulating osteoclast precursors are increased in number or have an increased sensitivity to humoral factors for osteoclastogenesis in breast cancer patients with skeletal metastases (± hypercalcaemia) compared to patients with primary breast cancer and age-matched normal controls. Monocytes were isolated and cocultured with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] and human macrophage colony stimulating factor (M-CSF) on coverslips and dentine slices. Limiting dilution experiments showed that there was no increase in the number of circulating osteoclast precursors in breast cancer patients with skeletal metastases (± hypercalcaemia) compared to controls. Osteoclast precursors in these patients also did not exhibit increased sensitivity to 1,25(OH)2D3 or M-CSF in terms of osteoclast formation. The addition of parathyroid hormone-related protein and interleukin-6 did not increase osteoclast formation. The addition of the supernatant of cultured breast cancer cell lines (MCF-7 and MDA-MB-435), however, significantly increased monocyte-osteoclast formation in a dose-dependent fashion. These results indicate that the increase in osteoclast formation in breast cancer is not due to an increase in the number/nature of circulating osteoclast precursors. They also suggest that tumour cells promote osteoclast formation in the bone microenvironment by secreting soluble osteoclastogenic factor(s). © 2001 Cancer Research Campaign http://www.bjcancer.com
癌症诱发高钙血症的机制。
DOI: --
发表时间: 1992
期刊: Laboratory investigation; a journal of technical methods and pathology
影响因子: --
作者:
Rosol,TJ;Capen,CC
通讯作者: Capen,CC
不同生长阶段自发转移瘤的巨噬细胞含量。
DOI: --
发表时间: 1987
期刊: Cancer research
影响因子: 11.2
作者:
Bugelski,PJ;Corwin,SP;North,SM;Kirsh,RL;Nicolson,GL;Poste,G
通讯作者: Poste,G