Breast cancer cell line MDA-MB 231 exerts a potent and direct anti-apoptotic effect on mature osteoclasts
Breast cancer cell line MDA-MB 231 exerts a potent and direct anti-apoptotic effect on mature osteoclasts
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DOI：
10.1016/j.bbrc.2004.05.033
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发表时间：
2004-06-25
影响因子：
3.1
通讯作者：
Kamel, S
中科院分区：
文献类型：
--
作者：
Gallet, M;Sévenet, N;Kamel, S
转移到骨的癌细胞刺激破骨细胞生成，导致骨破坏。然而，肿瘤细胞对完全分化的破骨细胞的影响却鲜为人知。我们假设乳腺癌细胞直接刺激成熟破骨细胞的存活。因此，我们测试了由 MDA-MB-231 细胞制备的条件培养基 (CM) 对从 10 日龄兔长骨中分离的破骨细胞活性和凋亡的影响。首先，我们证明了 CM 增加了兔成熟破骨细胞细胞模型中的骨吸收活性。使用高度纯化的破骨细胞细胞群，我们发现 MDA-MB-231 CM 显着抑制破骨细胞凋亡。在 20% CM 存在的情况下，细胞凋亡减少约 60%。 LY294002 是一种 PI3 激酶抑制剂，可强烈阻止 CM 的抗凋亡作用。人抗体中和实验表明，源自MDA-MB 231细胞的巨噬细胞集落刺激因子可能参与了CM的抗凋亡作用。这些结果表明，乳腺癌细胞除了刺激破骨细胞生成外，还能有效抑制成熟破骨细胞凋亡，这种机制可能极大地促进其溶骨潜力。 (C) 2004 Elsevier Inc. 保留所有权利。
Cancer cells metastasized to bone stimulate osteoclastogenesis resulting in bone destruction. However, the influence of tumor cells on fully differentiated osteoclasts is much less known. We postulated that breast cancer cells directly stimulate the survival of mature osteoclasts. We thus tested the effect of conditioned media (CM) prepared from MDA-MB-231 cells on the activity and apoptosis of osteoclasts isolated from 10-day-old rabbit long bones. First, we demonstrated that CM increased the bone resorbing activity in our cell model of rabbit mature osteoclasts. Using a highly purified osteoclast cell population, we found that MDA-MB-231 CM dramatically inhibited osteoclast apoptosis. In the presence of 20% CM, apoptosis was decreased by approximately 60%. LY294002, a PI3 kinase inhibitor, strongly prevented the CM anti-apoptotic effect. Neutralizing experiments with human antibody revealed that macrophage-colony stimulating factor originating from MDA-MB 231 cells was possibly involved in the CM antiapoptotic effect. These results suggest that breast cancer cells, in addition to stimulating osteoclastogenesis, potently inhibit mature osteoclast apoptosis, a mechanism which may greatly contribute to their osteolytic potential. (C) 2004 Elsevier Inc. All rights reserved.