Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous women's health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

[1]  Jingxin Ding,et al.  Gut and Vaginal Microbiomes in PCOS: Implications for Women’s Health , 2022, Frontiers in Endocrinology.

[2]  J. Schoones,et al.  The Human Vulvar Microbiome: A Systematic Review , 2021, Microorganisms.

[3]  C. Tarney,et al.  Human Papilloma Virus Vaccination , 2021, Viruses.

[4]  V. Holubekova,et al.  The interplay between the vaginal microbiome and innate immunity in the focus of predictive, preventive, and personalized medical approach to combat HPV-induced cervical cancer , 2021, EPMA Journal.

[5]  G. Hong,et al.  Diagnostic Value of Vaginal Microecology, Serum miR-18a, and PD-L1 for Identifying HPV-Positive Cervical Cancer , 2021, Technology in cancer research & treatment.

[6]  K. Hua,et al.  Types and viral load of human papillomavirus, and vaginal microbiota in vaginal intraepithelial neoplasia: a cross-sectional study , 2020, Annals of translational medicine.

[7]  J. Ravel,et al.  Bacterial Vaginosis and Its Association with Infertility, Endometritis, and Pelvic Inflammatory Disease. , 2020, American journal of obstetrics and gynecology.

[8]  R. McClelland,et al.  Association between Vaginal Bacterial Microbiota and Vaginal Yeast Colonization. , 2020, The Journal of infectious diseases.

[9]  K. Hua,et al.  Evaluation of a methylation classifier for predicting pre-cancer lesion among women with abnormal results between HPV16/18 and cytology , 2020, Clinical Epigenetics.

[10]  F. Abbas,et al.  Vaginal Microbiota and HPV Infection: Novel Mechanistic Insights and Therapeutic Strategies , 2020, Infection and drug resistance.

[11]  Ama Buskwofie,et al.  A Review of Cervical Cancer: Incidence and Disparities. , 2020, Journal of the National Medical Association.

[12]  P. Castle,et al.  Cervicovaginal microbiome and natural history of HPV in a longitudinal study , 2020, PLoS pathogens.

[13]  L. Engstrand,et al.  The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta‐analysis , 2019, BJOG : an international journal of obstetrics and gynaecology.

[14]  J. Ravel,et al.  The vaginal metabolome and microbiota of cervical HPV‐positive and HPV‐negative women: a cross‐sectional analysis , 2019, BJOG : an international journal of obstetrics and gynaecology.

[15]  E. Elinav,et al.  Vaginal microbiome transplantation in women with intractable bacterial vaginosis , 2019, Nature Medicine.

[16]  Ping Liu,et al.  Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome , 2019, Nature Medicine.

[17]  J. H. van de Wijgert,et al.  Vaginal dysbiosis and the risk of human papillomavirus and cervical cancer: systematic review and meta-analysis. , 2019, American journal of obstetrics and gynecology.

[18]  Hardik I. Parikh,et al.  The vaginal microbiome and preterm birth , 2019, Nature Medicine.

[19]  F. Bray,et al.  Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020-99: a modelling study. , 2019, The Lancet. Oncology.

[20]  Philipp W. Messer,et al.  The role of the vaginal microbiome in gynaecological cancer , 2018, BJOG : an international journal of obstetrics and gynaecology.

[21]  C. Lees,et al.  Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage , 2016, Science Translational Medicine.

[22]  R. Epstein.  VEGF signaling inhibitors: More pro-apoptotic than anti-angiogenic , 2007, Cancer and Metastasis Reviews.

[23]  E. Unger,et al.  Human Papillomavirus and Cervical Cancer , 2004, Emerging infectious diseases.

[24]  Anna-Barbara Moscicki,et al.  Does the vaginal microbiota play a role in the development of cervical cancer? , 2017, Translational research : the journal of laboratory and clinical medicine.