OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone
OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone
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DOI：
10.1002/ijc.29439
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发表时间：
2015-08-15
影响因子：
6.4
通讯作者：
Holen, Ingunn
中科院分区：
文献类型：
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作者：
Ottewell, Penelope D.;Wang, Ning;Holen, Ingunn
在原发肿瘤切除后数年，可在乳腺癌患者的骨髓中检测到背侧播散的肿瘤细胞。这些患者中的大多数将保持无症状，然而，类似于15%将继续发展明显的骨转移，并且这种情况目前无法治愈。为什么这些休眠细胞在某些患者中被刺激增殖并形成骨肿瘤，而在其他患者中却没有，其原因仍有待阐明。我们最近发现，在体内模型中，卵巢切除术增加骨转换刺激扩散的肿瘤细胞增殖，导致骨转移的形成。我们现在第一次表明破骨细胞介导的机制诱导肿瘤从散布在骨中的休眠MDA-MB-231细胞生长。我们还表明，OPG-Fc给药后RANK-RANKL相互作用的破坏可抑制这些休眠肿瘤细胞的体内生长。我们的数据支持在低雌激素环境下进行抗吸收治疗的早期干预，以防止骨转移的发生。
Dormant disseminated tumour cells can be detected in the bone marrow of breast cancer patients several years after resection of the primary tumour. The majority of these patients will remain asymptomatic, however, similar to 15% will go on to develop overt bone metastases and this condition is currently incurable. The reason why these dormant cells are stimulated to proliferate and form bone tumours in some patients and not others remains to be elucidated. We have recently shown that in an in vivo model, increasing bone turnover by ovariectomy stimulated proliferation of disseminated tumour cells, resulting in formation of bone metastasis. We now show for the first time that osteoclast mediated mechanisms induce growth of tumours from dormant MDA-MB-231 cells disseminated in the bone. We also show that disruption of RANK-RANKL interactions following administration of OPG-Fc inhibits growth of these dormant tumour cells in vivo. Our data support early intervention with anti-resorptive therapy in a low-oestrogen environment to prevent development of bone metastases.