Two on one
Women who develop cervical cancer are often infected not only with the human papillomavirus (HPV), but also with the bacterium Chlamydia trachomatis. Therefore, it is suspected that these two pathogens work together to rebuild infected cells into cancerous ones. Dr. Sindrilla Chumduri, head of the research team at the Julius Maximilian University of Würzburg (JMU), demonstrated for the first time that this is not just a suspicion, but a proven effect.
Using cells from healthy donors, the group created three-dimensional cervical organoids, on which they studied the interaction of pathogens with tissues and developing pathological processes.
The main conclusion: concomitant infections alter cells, forming a unique cellular microenvironment that potentially promotes tissue degeneration and, consequently, the development of cancer.
The researchers focused on two types of tissues: ectocervix – parts of the mucous membrane of the external part of the cervix, and endocervix – parts of the mucous membrane of the internal part of the cervix, passing into the uterus. The main function of these tissues is to prevent pathogenic microorganisms from entering the uterus and, thus, to preserve the sterility of the upper parts of the female reproductive system. The area where the ectocervix borders the endocervix is called the transition zone and is particularly susceptible to infections and neoplasms; most cases of cervical cancer are localized in it.
HPV and C.trachomatis are among the most common sexually transmitted infections. It has already been proven that HPV can cause cancer, and in Germany, for example, children have been vaccinated against it since 2007.
Viral DNA is found in more than 90% of cases of cervical cancer. However, HPV is not the only cause of the disease, because more than 80% of women are infected with it, and less than 2% of them develop cancer. Therefore, it is assumed that coinfection of C.trachomatis is the main factor stimulating the formation of malignant tissues. However, the dynamics of this cooperation and the underlying mechanisms were largely unknown.
The problem is that unlike viruses, whose DNA can be found in tumors, cancer-related bacteria rarely leave detectable elements in cancer cells. To link bacteria to cancer risk, it is necessary to identify cellular and mutational processes that contribute to cell degeneration. Chumduri and her group systematically analyzed exactly these processes in the organoids they created from the cells of patients.
Three-dimensional organoids of tissues affected by cervical cancer helped demonstrate the joint role of HPV and C.trachomatis in reprogramming host cells. The researchers found that some genes are regulated differently by both pathogens, including a significant subset of genes responsible for DNA damage repair. In general, the results obtained show that the joint persistence of HPV and chlamydia can negatively affect cellular and genomic stability and contribute to tumor progression.
Green – squamous cell carcinoma cells, red – uterine tissue cells infected with chlamydia.
At the same time, the study demonstrated the effectiveness of cervical organoids developed by Chumduri's group for studying various biological aspects, including drug testing under almost physiological conditions. The cultivability of these organoids and the possibility of genetic manipulation of them open up new opportunities for studying the development, progression and outcome of chronic infections in preclinical conditions.
Article by S.Koster et al. Modeling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Universität Würzburg: Cancer: When viruses and bacteria cooperate.