Osteoncology Center, Cancer Institute of Romagna, I.R.S.T., [corrected] Meldola, Italy.
Cancer. 2010 Mar 15;116(6):1406-18. doi: 10.1002/cncr.24896.
Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells.
前列腺癌是男性癌症相关死亡的第二大主要原因。这种疾病的一个典型特征是其向骨骼转移的能力。它主要是成骨性的，是由成骨细胞活性相对过剩引起的，导致异常的骨形成。骨转移是一系列复杂步骤的结果，这些步骤尚未完全理解，并且依赖于转移性癌细胞、骨髓微环境的细胞成分和骨基质（成骨细胞和破骨细胞）之间的动态串扰。来自原发性组织的前列腺癌细胞经历上皮-间充质转化以扩散并获得类似骨的表型，从而在骨组织中转移。这篇综述讨论了骨转移进展中涉及的生物学过程和分子。在这里，我们重点讨论成骨细胞分化和激活的途径、骨细胞和肿瘤细胞之间的串扰以及成骨细胞和肿瘤细胞表达的这些过程中涉及的分子。此外，本综述还涉及最近阐明的破骨细胞在前列腺癌骨转移中的作用。当然，为了更好地理解骨转移的潜在机制，从而改善针对骨的治疗方法，需要进一步的研究来阐明前转移龛的可能作用以及癌症干细胞的参与。
