Bleeker Joosje, Wang Zhu A
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, United States.
Front Mol Biosci. 2022 Jul 5;9:898871. doi: 10.3389/fmolb.2022.898871. eCollection 2022.
It has long been postulated that the inflammatory environment favors cell proliferation, and is conducive to diseases such as cancer. In the prostate gland, clinical data implicate important roles of prostatitis in the progression of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). However, their causal relationships have not been firmly established yet due to unresolved molecular and cellular mechanisms. By accurately mimicking human disease, vertebrate animals provide essential models to address this question. Here, we review the vertebrate prostatitis models that have been developed and discuss how they may reveal possible mechanisms by which prostate inflammation promotes BPH and PCa. Recent studies, particularly those involving genetically engineered mouse models (GEMMs), suggest that such mechanisms are multifaceted, which include epithelium barrier disruption, DNA damage and cell proliferation induced by paracrine signals, and expansion of potential cells of origin for cancer. Future research using rodent prostatitis models should aim to distinguish the etiologies of BPH and PCa, and facilitate the development of novel clinical approaches for prostatic disease prevention.
长期以来,人们一直推测炎症环境有利于细胞增殖,并易引发癌症等疾病。在前列腺中,临床数据表明前列腺炎在良性前列腺增生(BPH)和前列腺癌(PCa)的进展中起重要作用。然而,由于尚未解决的分子和细胞机制,它们之间的因果关系尚未得到确凿证实。通过精确模拟人类疾病,脊椎动物提供了重要模型来解决这个问题。在这里,我们回顾已开发的脊椎动物前列腺炎模型,并讨论它们如何揭示前列腺炎症促进BPH和PCa的可能机制。最近的研究,特别是那些涉及基因工程小鼠模型(GEMMs)的研究表明,这些机制是多方面的,包括上皮屏障破坏、旁分泌信号诱导的DNA损伤和细胞增殖,以及癌症潜在起源细胞的扩增。未来使用啮齿动物前列腺炎模型的研究应旨在区分BPH和PCa的病因,并促进前列腺疾病预防新临床方法的开发。