Yu Chunyan, Shiozawa Yusuke, Taichman Russell S, McCauley Laurie K, Pienta Kenneth, Keller Evan
Department of Urology, School of Medicine, University of Michigan, Ann Arbor, MI 48109-0940, USA.
Crit Rev Eukaryot Gene Expr. 2012;22(2):131-48. doi: 10.1615/critreveukargeneexpr.v22.i2.50.
A subpopulation of men that appear cured of prostate cancer (PCa) develop bone metastases many years after prostatectomy. This observation indicates that PCa cells were present outside of the prostate at the time of prostatectomy and remained dormant. Several lines of evidence indicate that there are disseminated tumor cells (DTCs) in the bone marrow at the time of prostatectomy. DTCs parasitize the bone microenvironment, where they derive support and impact the microenvironment itself. These DTCs appear to be a heterogeneous population of PCa cells; however, some of them appear to have some aspects of a cancer stem cell (CSC) phenotype as they can develop into clinically detectable metastases. The concept of CSC is controversial; however, several markers of CSC have been identified for PCa, which may represent cells of either basal or luminal origin. These DTCs have now been shown to compete for the hematopoietic stem cell niche in bone, where they may be placed in a dormant state. Interaction with a variety of host factors, including cytokine and cells, may impact the metastatic development and progression, including the dormant state. For example, myeloid cells have been shown to impact both the premetastatic niche and established tumors. Understanding the concepts of how PCa successfully parasitizes the bone microenvironment is paramount toward identifying therapeutic candidates to prevent or diminish PCa bone metastases.
一部分看似已治愈前列腺癌（PCa）的男性在前列腺切除术后多年出现骨转移。这一观察结果表明，前列腺癌细胞在前列腺切除时已存在于前列腺之外，并处于休眠状态。多项证据表明，前列腺切除时骨髓中存在播散肿瘤细胞（DTCs）。DTCs寄生于骨微环境中，在那里它们获得支持并影响微环境本身。这些DTCs似乎是异质性的前列腺癌细胞群体；然而，其中一些似乎具有癌症干细胞（CSC）表型的某些特征，因为它们可以发展为临床可检测到的转移灶。CSC的概念存在争议；然而，已经为PCa鉴定出几种CSC标志物，它们可能代表基底或管腔来源的细胞。现已证明，这些DTCs会竞争骨中的造血干细胞龛位，在那里它们可能处于休眠状态。与包括细胞因子和细胞在内的多种宿主因子相互作用，可能会影响转移的发生和进展，包括休眠状态。例如，髓样细胞已被证明会影响转移前龛位和已形成的肿瘤。了解PCa如何成功寄生于骨微环境的概念对于确定预防或减少PCa骨转移的治疗候选药物至关重要。
