Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637, USA;
Cancers (Basel). 2011;3(1):478-93. doi: 10.3390/cancers3010478.
Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.
骨骼是人前列腺癌患者中转移最常见的部位。骨骼转移是发病率和死亡率的重要原因，总体上极大地影响了前列腺癌患者的生活质量。尽管我们对原发性前列腺肿瘤的生物学有了更多的了解，但我们对前列腺癌细胞衍生的继发性肿瘤如何以及为何优先定位于骨骼的了解仍然有限。骨骼的物理化学特性，以及包括特定趋化因子及其受体在内的信号分子，在性质和功能上是不同的，但在前列腺癌骨转移中起着错综复杂且重要的作用。在体内研究这些骨转移方面的影响仍然是一个重大挑战，因为能够模拟临床前列腺癌自然史和恶性进展的动物模型非常罕见。本文的目的是讨论：（1）最有可能使骨骼成为有利于前列腺肿瘤细胞生长的环境的特征；（2）在招募和迁移前列腺癌细胞到骨骼中起关键作用的趋化因子信号；（3）目前用于研究前列腺癌骨转移的动物模型。需要进一步的研究来阐明播散的前列腺癌细胞进入骨骼的机制，并更好地理解癌细胞在骨骼微环境中存活的基础。开发更能重现人类前列腺癌临床情况的动物模型将极大地促进更好的治疗方法的产生。
