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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases
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A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases

机译:内皮素-1在成骨细胞骨转移发病机理中的因果关系

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摘要

Osteoblastic bone metastases are common in prostate and breast cancer patients, but mechanisms by which tumor cells stimulate new bone formation are unclear. We identified three breast cancer cell lines that cause osteoblastic metastases in a mouse model and secrete endothelin-1. Tumor-produced endothelin-1 stimulates new bone formation in vitro and osteoblastic metastases in vivo via the endothelin A receptor. Treatment with an orally active endothelin A receptor antagonist dramatically decreased bone metastases and tumor burden in mice inoculated with ZR-75-1 cells. Tumor-produced endothelin-1 may have a major role in the establishment of osteoblastic bone metastases, and endothelin A receptor blockade represents effective treatment. [References: 42]
机译:成骨细胞的骨转移在前列腺癌和乳腺癌患者中很常见,但是尚不清楚肿瘤细胞刺激新骨形成的机制。我们鉴定了三种导致小鼠模型中成骨细胞转移并分泌内皮素-1的乳腺癌细胞系。肿瘤产生的内皮素-1通过内皮素A受体刺激体外新骨形成和体内成骨细胞转移。用口服活性内皮素A受体拮抗剂治疗可显着降低接种ZR-75-1细胞的小鼠的骨转移和肿瘤负担。肿瘤产生的内皮素-1可能在成骨细胞骨转移的建立中起主要作用,而内皮素A受体阻滞代表有效的治疗方法。 [参考:42]

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