Ability of breast cancer cell lines to stimulate bone resorbing activity of mature osteoclasts correlates with an anti-apoptotic effect mediated by macrophage colony stimulating factor
Ability of breast cancer cell lines to stimulate bone resorbing activity of mature osteoclasts correlates with an anti-apoptotic effect mediated by macrophage colony stimulating factor
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DOI：
10.1007/s10495-006-9507-z
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发表时间：
2006-11-01
期刊：
影响因子：
7.2
通讯作者：
Kamel, Said
中科院分区：
文献类型：
--
作者：
Gallet, Marlene;Mentaverri, Romuald;Kamel, Said
我们比较了几种人乳腺癌细胞系条件培养基（CM）对破骨细胞骨吸收活性和破骨细胞凋亡的影响。我们的研究结果表明，癌细胞增加体外骨吸收活性的能力与其抑制破骨细胞凋亡的潜力有关。产生更高水平M-CSF的癌细胞具有更高的溶骨活性，这表明来自癌细胞的M-CSF可能通过提高转移部位的破骨细胞的存活率，至少部分地促进了破骨细胞的活性。鉴于M-CSF在抗凋亡作用中发挥重要作用，我们推测阻断M-CSF通路可阻止CM作用。靶向M-CSF的小干扰RNA （siRNA）和靶向M-CSF受体的蛋白酪氨酸激酶抑制剂伊马替尼（imatinib）几乎完全逆转了CM对破骨细胞凋亡和骨吸收的影响。因此，阻断M-CSF通路可能在治疗乳腺癌相关骨破坏方面具有临床价值。
We compared the effect of conditioned medium (CM) from several human breast carcinoma cell lines on osteoclast bone resorbing activity and osteoclast apoptosis. Our findings indicate that ability of cancer cell line to increase the in vitro bone resorbing activity is linked to their potential to inhibit osteoclast apoptosis. Cancer cells producing the higher level of M-CSF have the higher osteolytic activity, suggesting that M-CSF originating from cancer cells may contribute, at least in part, to the osteoclast activity at the metastatic site by enhancing their survival. Given that M-CSF plays an important role in the anti-apoptotic effect, we speculated that blocking M-CSF pathway would prevent the CM effects. Small interfering RNA (siRNA) targeting M-CSF and imatinib, a protein tyrosine kinase inhibitor targeting M-CSF receptor, almost completely reversed the CM effect on both osteoclast apoptosis and bone resorption. Blockade of M-CSF pathway could be thus of clinical value in the treatment of breast cancer related bone destruction.