CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro
CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro
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DOI：
10.1111/j.1474-9726.2005.00173.x
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发表时间：
2005-12-01
期刊：
影响因子：
7.8
通讯作者：
Macoska, JA
中科院分区：
文献类型：
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作者：
Begley, L;Monteleon, C;Macoska, JA
衰老过程与良性前列腺增生（BPH）和前列腺癌（PCa）的发病率和患病率之间的直接关系意味着与这两种疾病的发展相关的某些风险因素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，表明正常情况下抑制细胞增殖的机制由于衰老过程而被破坏或功能失调。我们提出，这样的机制之一涉及前列腺微环境的变化，这在衰老过程中“进化”，并破坏上皮细胞和相关的基质成纤维细胞之间的旁分泌相互作用。我们发现，与从年轻男性中分离的成纤维细胞相比，从63-81岁男性前列腺中分离的手术时的基质成纤维细胞表达和分泌更高水平的CXCL 12趋化因子，并刺激CXCR 4介导的诱导细胞增殖的信号通路。这些研究代表了对良性和恶性前列腺疾病的病因老化的作用的机制阐明的重要的第一步。
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.