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痤疮丙酸杆菌在病变前列腺组织中的流行情况及其对前列腺上皮细胞的炎症和转化活性。

Prevalence of Propionibacterium acnes in diseased prostates and its inflammatory and transforming activity on prostate epithelial cells.

机构信息

Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, D-10117 Berlin, Germany.

出版信息

Int J Med Microbiol. 2011 Jan;301(1):69-78. doi: 10.1016/j.ijmm.2010.08.014. Epub 2010 Oct 12.

Abstract

Prostate cancer (PCa) is the second leading cause of male cancer deaths in the Western world. Mounting evidence has revealed that chronic inflammation can be an important initiating factor of PCa. Recent work has detected the anaerobic Gram-positive bacterium Propionibacterium acnes in cancerous prostates, but with wide-ranging detection rates. Here, using in situ immunofluorescence (ISIF), P. acnes was found in 58 out of 71 (81.7%) tested cancerous prostate tissue samples, but was absent from healthy prostate tissues (20 samples) and other cancerous tissue biopsies (59 mamma carcinoma samples). Live P. acnes bacteria were isolated from cancerous prostates and cocultured with the prostate epithelial cell line RWPE1. Microarray analysis showed that the host cell responded to P. acnes with a strong multifaceted inflammatory response. Active secretion of cytokines and chemokines, such as IL-6 and IL-8, from infected cells was confirmed. The host cell response was likely mediated by the transcriptional factors NF-κB and STAT3, which were both activated upon P. acnes infection. The P. acnes-induced host cell response also included the activation of the COX2-prostaglandin, and the plasminogen-matrix metalloproteinase pathways. Long-term exposure to P. acnes altered cell proliferation, and enabled anchorage-independent growth of infected epithelial cells, thus initiating cellular transformation. Our results suggest that P. acnes infection could be a contributing factor to the initiation or progression of PCa.

摘要

前列腺癌(PCa)是西方男性癌症死亡的第二大主要原因。越来越多的证据表明,慢性炎症可能是 PCa 的一个重要起始因素。最近的研究在癌变前列腺中检测到了厌氧革兰阳性菌痤疮丙酸杆菌,但检测率差异很大。在这里,通过原位免疫荧光(ISIF)检测,在 71 个测试的癌变前列腺组织样本中发现 58 个(81.7%)存在痤疮丙酸杆菌,但在健康前列腺组织(20 个样本)和其他癌变组织活检(59 个乳腺癌样本)中不存在。从癌变前列腺中分离出活的痤疮丙酸杆菌,并与前列腺上皮细胞系 RWPE1 共培养。微阵列分析显示,宿主细胞对痤疮丙酸杆菌产生了强烈的多方面炎症反应。证实了受感染细胞中细胞因子和趋化因子(如 IL-6 和 IL-8)的主动分泌。宿主细胞的反应可能是由转录因子 NF-κB 和 STAT3 介导的,这两种转录因子在痤疮丙酸杆菌感染后均被激活。痤疮丙酸杆菌诱导的宿主细胞反应还包括 COX2-前列腺素和纤溶酶原-基质金属蛋白酶途径的激活。长期暴露于痤疮丙酸杆菌会改变细胞增殖,并使受感染的上皮细胞能够进行无锚定生长,从而引发细胞转化。我们的研究结果表明,痤疮丙酸杆菌感染可能是 PCa 发生或进展的一个促成因素。

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