Platelets govern pre-metastatic tumor communication to bone.

Platelets govern pre-metastatic tumor communication to bone.
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DOI:
10.1038/onc.2012.447
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发表时间:
2013-09-05
期刊:
影响因子:
8
通讯作者:
Byzova, T. V.
Byzova, T. V.
中科院分区:
医学1区
文献类型:
--
作者:
Kerr, B. A.;McCabe, N. P.;Feng, W.;Byzova, T. V.

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虽然早期发现的癌症的存活率很高,但一旦癌症转移到骨骼,就无法治愈。有趣的是,没有可见转移的患者显示异常的骨形成和再吸收,表明原发性癌症和转移前的骨微环境之间存在联系,这种联系可能有助于转移前小生境的准备。我们假设原发肿瘤的通讯会导致骨重建改变,血小板可以促进这种通讯。使用三种肿瘤模型,我们证明了原发性肿瘤生长刺激骨形成测量的微型计算机断层扫描(microCT)。此外,血小板耗竭阻止了肿瘤诱导的骨形成,突出了血小板在肿瘤和骨微环境之间的沟通中的重要性。最后,我们确定血小板隔离多种肿瘤衍生蛋白,特别是TGF-β1和MMP-1,它们调节骨形成。因此,我们的数据表明,血小板的功能作为介质的肿瘤骨通讯转移前。
While the survival rate for early detected cancers is high, once a cancer metastasizes to bone, it is incurable. Interestingly, patients without visible metastases display abnormal bone formation and resorption suggesting a link between primary cancers and the bone microenvironment prior to metastasis and this link likely facilitates preparation of the pre-metastatic niche. We hypothesized that communication from the primary tumor would result in bone remodeling alterations and that platelets could facilitate this communication. Using three tumor models, we demonstrate that primary tumor growth stimulates bone formation measured by microcomputed tomography (microCT). Further, platelet depletion prevented tumor-induced bone formation highlighting the importance of platelets in the communication between tumors and the bone microenvironment. Finally, we determine that platelets sequester a variety of tumor-derived proteins, TGF-β1 and MMP-1 in particular, which regulate bone formation. Thus, our data reveals that platelets function as mediators of tumor-bone communication prior to metastasis.
在两个骨转移动物模型中,微环境与癌细胞之间的相互作用。
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