甲磺酸伊马替尼抑制乳腺癌的骨转移通过抑制破骨细胞通过封锁c-Fms信号。
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中村Hiraga T H
甲磺酸伊马替尼抑制乳腺癌的骨转移通过抑制破骨细胞通过封锁c-Fms信号。
Int J癌症。2009年1月1;124(1):215 - 22所示。doi: 10.1002 / ijc.23903。
- PubMed ID
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18814279 (在PubMed]
- 文摘
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甲磺酸伊马替尼(伊马替尼)是一种强有力的和选择性的酪氨酸激酶抑制剂,bcr - abl、c - kit和血小板源生长因子受体(pdgfr)。最近,据报道,伊马替尼也巨噬细胞集落刺激因子(csf)受体c-Fms目标。csf对破骨细胞的分化信号是至关重要的。乳腺癌骨转移经常与监测相关的骨破坏。此外,一些证据表明,破骨细胞发挥核心作用在骨转移的开发和发展。因此,在目前的研究中,我们调查了伊马替尼对乳腺癌骨转移的影响。Coimmunoprecipitation化验表明,伊马替尼抑制c-Fms M-CSF-induced磷酸化的破骨细胞前体细胞以及PDGF-induced PDGFR磷酸化在人类乳腺癌mda - mb - 231细胞。伊马替尼也显著降低体外破骨细胞的形成。相比之下,伊马替尼的浓度没有影响成骨细胞的分化。然后我们调查了伊马替尼对骨转移的影响的mda - mb - 231细胞在裸鼠模型。 Radiographic and histomorphometric analyses demonstrated that imatinib significantly decreased bone metastases associated with the reduced number of osteoclasts. In support of the notion that the inhibition of c-Fms acts to suppress the development of bone metastases, we found that a specific inhibitor of c-Fms Ki20227 also decreased bone metastases. In conclusion, these results collectively suggest that imatinib reduced bone metastases, at least in part, by inhibiting osteoclastic bone destruction through the blockade of c-Fms signals. Our results also suggest that imatinib may have a protective effect against cancer treatment-induced bone loss.