Cells of Origin for Prostate Cancer
Cells of Origin for Prostate Cancer
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DOI：
10.1007/978-3-030-32656-2_4
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Xin, Li
中科院分区：
文献类型：
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作者：
Xin, Li
全面了解正常前列腺上皮细胞谱系是研究前列腺癌起源细胞身份的先决条件。基底细胞和腔细胞构成了前列腺上皮的大部分，并且一直是前列腺癌起源细胞研究的主要焦点。在过去的几十年里，主要是使用小鼠模型，已经取得了很大的进展，以了解谱系间的关系和谱系内的异质性，以及在压力条件下的谱系可塑性。这些研究得出结论，成年小鼠前列腺基底细胞和腔细胞在生理条件下基本上是独立维持的，但这两种类型的细胞在应激或人工实验条件下都具有双能分化的能力。然而，每个谱系中假定的祖先的存在或身份需要进一步调查。人类前列腺谱系层级是否与小鼠完全相同仍不确定。来自独立小组的实验已经证明，小鼠和人类的两种类型的细胞都可以作为转化的目标。但是对于不同来源细胞的疾病是否表现出不同的临床行为仍存在争议。对谱系内异质性的进一步研究将为这一问题提供新的见解。了解前列腺癌起源细胞的身份将有助于识别早期检测侵袭性前列腺癌的新预后标志物，为这些肿瘤的治疗脆弱性提供见解，并激发新的治疗策略。
Comprehensive knowledge of the normal prostate epithelial lineage hierarchy is a prerequisite to investigate the identity of the cells of origin for prostate cancer. The basal and luminal cells constitute most of the prostate epithelium and have been the major focuses of the study on the cells of origin for prostate cancer. Much progress has been made during the past few decades, mainly using mouse models, to understand the inter-lineage relationship and intra-lineage heterogeneity in adults as well as the lineage plasticity during conditions of stress. These studies have concluded that the adult mouse prostate basal and luminal cells are largely independently sustained under physiological conditions, but both types of cells possess the capacity for bipotent differentiation under stress or artificial experimental conditions. However, the existence or the identity of the putative progenitors within each lineage warrants further investigation. Whether the human prostate lineage hierarchy is completely the same as that of the mouse remains uncertain. Experiments from independent groups have demonstrated that both types of cells in mice and humans can serve as targets for transformation. But controversies remain whether the disease from distinct cells of origin display different clinical behaviors. Further investigation of the intra-lineage heterogeneity will provide new insights into this issue. Understanding the identity of the cells of origin for prostate cancer will help identify novel prognostic markers for early detection of aggressive prostate cancers, provide insights into the therapeutic vulnerability of these tumors, and inspire novel therapeutic strategies.