Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA.
Oncogene. 2013 Sep 5;32(36):4319-24. doi: 10.1038/onc.2012.447. Epub 2013 Sep 15.
Although 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 with the primary tumor would result in bone remodeling alterations, and that platelets could facilitate this communication. By using three tumor models, we demonstrate that primary tumor growth stimulates bone formation measured by microcomputed tomography. 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 reveal that platelets function as mediators of tumor-bone communication prior to metastasis.
尽管早期发现的癌症存活率很高，但一旦癌症转移到骨骼，就无法治愈。有趣的是，没有明显转移的患者表现出异常的骨形成和吸收，这表明原发性癌症与转移前的骨骼微环境之间存在联系，这种联系可能有助于准备转移前的生态位。我们假设与原发性肿瘤的交流将导致骨骼重塑的改变，而血小板可以促进这种交流。通过使用三种肿瘤模型，我们证明了原发性肿瘤的生长刺激了微计算机断层扫描测量的骨形成。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与骨骼微环境之间的交流中的重要性。最后，我们确定血小板隔离了多种肿瘤衍生蛋白，特别是 TGF-β1 和 MMP-1，它们调节骨形成。因此，我们的数据表明，血小板在转移前充当肿瘤-骨骼通讯的介质。
