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

被引:115
|
作者
Fehri, Lina Fassi [1 ]
Mak, Tim N. [1 ]
Laube, Britta [2 ]
Brinkmann, Volker [2 ]
Ogilvie, Lesley A. [1 ]
Mollenkopf, Hans [3 ]
Lein, Michael [4 ]
Schmidt, Timo [4 ]
Meyer, Thomas F. [1 ]
Brueggemann, Holger [1 ]
机构
[1] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany
[2] Max Planck Inst Infect Biol, Imaging Core Facil, D-10117 Berlin, Germany
[3] Max Planck Inst Infect Biol, Microarray Core Facil, D-10117 Berlin, Germany
[4] Univ Hosp Charite, Dept Urol, D-10117 Berlin, Germany
关键词
Propionibacterium acnes; Chronic inflammation; Prostate cancer; Cellular transformation; Infection and cancer; INDUCED MALIGNANT TRANSFORMATION; NF-KAPPA-B; CANCER CELLS; CONSTITUTIVE ACTIVATION; ANDROGEN RECEPTOR; IN-VITRO; STAT3; PATHWAY; GROWTH; RISK;
D O I
10.1016/j.ijmm.2010.08.014
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-kappa B 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. (C) 2010 Elsevier GmbH. All rights reserved.
引用
收藏
页码:69 / 78
页数:10
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