Begley Lesa, Monteleon Christine, Shah Rajal B, Macdonald James W, Macoska Jill A
Department of Urology, The University of Michigan, Ann Arbor, 48109, USA.
Aging Cell. 2005 Dec;4(6):291-8. doi: 10.1111/j.1474-9726.2005.00173.x.
The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63-81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.
衰老过程与良性前列腺增生（BPH）和前列腺癌（PCa）的发病率及患病率之间的直接关系表明，与这两种疾病发生相关的某些风险因素会随着衰老过程而增加。特别是，这两种疾病都具有过度增殖的表型，这表明正常情况下抑制细胞增殖的机制会因衰老过程而被破坏或功能失调。我们提出，一种这样的机制涉及前列腺微环境的变化，这种微环境在衰老过程中“演变”并破坏上皮细胞与相关基质成纤维细胞之间的旁分泌相互作用。我们发现，与从较年轻男性中分离出的基质成纤维细胞相比，在手术时从63至81岁男性前列腺中分离出的基质成纤维细胞表达并分泌更高水平的CXCL12趋化因子，并刺激CXCR4介导的诱导细胞增殖的信号通路。这些研究是朝着从机制上阐明衰老在良性和恶性前列腺疾病病因学中的作用迈出的重要第一步。
