Persistent Exposure to Mycoplasma Induces Malignant Transformation of Human Prostate Cells

Kazunori Namiki,Kenneth A Iczkowski,Steve Goodison,Leticia Reyes,Noboru Sakamoto,Cydney Urbanek,Charles J Rosser,Holger Bruggemann,Robert W Allan,Stacy Porvasnik

doi:10.1371/journal.pone.0006872

Abstract

Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1) was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.

Highlights

Mycoplasma, a class of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time [1]
BPH-1 cells were infected with M. genitalium or M. hyorhinis and maintained in continuous culture for 20 weeks
In vitro migration and invasion assays We have previously published that in a dose-dependent manner, p37 increases tumor cell migration and invasion in both PC-3 and DU145 cancer cells [16,17]. To investigate whether this phenomenon can be replicated with mycoplasma, we evaluated the migratory and invasive potential of BPH-1, with or without the presence of M. hyorhinis or M. genitalium, over the course of the 19 weeks of infection

Summary

Introduction

Mycoplasma, a class of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time [1]. Due to the fastidious nature of mycoplasma, it is often difficult to isolate the organism from human specimens or the study implements a molecular amplification approach for its detection [2]. M. genitalium has been identified as the cause of non-gonococcal urethritis in approximately 15–22% of symptomatic men [3,4,5]. Several studies have linked M. genitalium with chronic persistent prostatitis [7,8]

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Conclusion