Endogenous Propionibacterium acnes Promotes Ovarian Cancer Progression via Regulating Hedgehog Signalling Pathway

Abstract

Background: The oncogenesis and progression of epithelial ovarian cancer (EOC) is a complicated process involving several key molecules and factors, yet whether microbiota are present in EOC, and their role in the development of EOC, remains greatly unknown. Methods: In this study, 30 patients were enrolled to compare the similarities and differences of intratumour microbiota among patients with epithelial benign ovarian tumours (EBOTs) and patients with EOC based on the high-throughput sequencing method. Subsequently, we further isolated the specific EOC-related bacteria and defined Propionibacterium acnes as a key strain in facilitating EOC progression. More importantly, we constructed a mouse EOC model to evaluate the effect of the P. acnes strain on EOC using immunohistochemistry, Western blotting, and RT-qPCR. Results: The high-throughput sequencing showed that the intratumour microbiota in EOC tissues had a higher microbial diversity and richness compared to EBOT tissues. The abundance of previously considered pathogens, Actinomycetales, Acinetobacter, Streptococcus, Ochrobacterium, and Pseudomonadaceae Pseudomonas, was increased in the EOC tissues. Meanwhile, we discovered the facilitating role of the P. acnes strain in the progression of EOC, which may be partially associated with the increased inflammatory response to activate the hedgehog (Hh) signalling pathway. This microbial-induced EOC progression mechanism is further confirmed using the inhibitor GANT61. Conclusions: This study profiled the intratumour microbiota of EBOT and EOC tissues and demonstrated that the diversity and composition of the intratumour microbiota were significantly different. Furthermore, through in vivo and in vitro experiments, we confirmed the molecular mechanism of intratumour microbiota promotion of EOC progression in mice, which induces inflammation to activate the Hh signalling pathway. This could provide us clues for improving EOC treatment.

Endogenous Microbacteria Can Contribute to Ovarian Carcinogenesis by Reducing Iron Concentration in Cysts: A Pilot Study

“…It is believed that these changes could be linked to the severity of Cervical Intraepithelial Neoplasia (CIN), with an increase in Bacillus and Anaerococcus and a decrease in Gardnerella vaginalis potentially indicating a greater severity of the condition [ 36 ]. There are some studies suggesting that Propionibacterium acnes contributes to the development of several diseases in the prostate [ 37 ], gastric cancer [ 38 ], and ovarian cancer via regulating the hedgehog signaling pathway [ 32 ]. In this study, it was suggested that the genus level of Propionibacterium may be responsible for converting the cyst fluid environment to an environment with a lower concentration of iron.…”

Gynecological Cancers and Microbiota Dynamics: Insights into Pathogenesis and Therapy

“…In addition, intratumoral Propionibacterium acnes found in ovarian cancer tissue seems to play a key role in cancer progression by aberrant hedgehog signaling activation [111]. In vitro studies have demonstrated that the original bacterial molecule, such as lipopolysaccharide Escherichia coli, can induce the release of pro-inflammatory cytokines in ovarian cancer cells, promoting tumor growth and chemo-resistance through the stimulation of TLR (toll-like receptor) receptors [112].…”

Vaginal microbiota and gynecological cancers: a complex and evolving relationship

“…The study discovered that the P . acnes strain had a significant impact on the development of EOC [ 84 ].…”