Modern Medical Laboratory Journal

Infectious agents cause 15-20% of cancers all around the world (1,2). The contamination of infectious agents may be caused by a local chronic inflammatory response, or by tumorization through viral or bacterial protein products (3-5). Different types of infectious agents have been identified for various cancers (6). Mycoplasma contamination can interfere with biological agents and cause DNA damage which affects gene expression, disrupts the cell-cycle control and apoptotic responses (7-9). M. hyorhinis can increase the invasion and migration of prostate epithelial cells which is associated with arthritis, cervicitis, infertility and human cancer that is a common contamination of stem cells (10–14). M. hyorhinis belongs to the class Mollicutes that are small and wall-free. In the 1960s, the first study has reported the association between mycoplasma infection and leukemia (15).
It has been reported that M. hyorhinis is the most usual contamination of cell cultures in association with human cancers, such as (esophageal, gastric, lung, breast, glioma, colon cancer, and prostate) (10, 16-17). Namiki and colleagues reported the occurrence of M. hyorhinis infection in malignant of the benign human prostate (BPH-1) in cell culture (10, 17-18). Besides, Urbanek and his colleagues, using serological test showed positive tests of M. hyorhinis for more than thirty percent benign prostatic hyperplasia (BPH) and more than fifty percent prostatic cancer tissues (19). Moreover, these bacteria are able to increases the cell migration and cell invasion of gastric cancer cells and melanoma cells (10, 16-17).
Dong and his research group in 1980 performed studies on monoclonal PD4 antibody via mice immunization with the gastric cancer cell, then the mycoplasma antigen was detected by PD4, which is a lipoprotein of M. hyorhinis called P37 and does not have any homology with human proteins (17-21).
In a study by Huang et al., using this antibody for immunohistochemistry, the prevalence of the mycoplasma species was evaluated in tissues, the prevalence of this bacterium was more than fifty percent in gastric cancer, twenty-eight percent in chronic superficial gastritis, thirty percent in gastric ulcer and thirty-seven percent in intestinal metaplasia. However, in colon cancer, the prevalence was fifty percent but 20% reported in the adenomatous polyp, which showed the increased prevalence of M. hyorhinis as a disease progressive (16).
The study of Duan displayed that this mycoplasma infection depends on the interaction of p37 protein, which is a major membrane protein of M. hyorhinis and host ANXA2 through the N-terminal. Also, polyclonal antibodies can block p37 and cause decreasing contamination and promoting the migration of M. hyorhinis from the gastric cancer cell, respectively (22). 
Studies have shown a direct interaction between the mycoplasma contamination and cancer metastasis such that p37 invasion and metastatic gastric cancer cells will increase both in vitro and in vivo (19, 23).
 
M. hyorhinis in different tissues
Information related to data collection from different cancer registries via M. hyorhinis have been published in various articles (Table1). In 1995, in their first study, Sasaki et al. reported a high prevalence of mycoplasmas in tumor tissue and found 48% of gastric adenocarcinoma samples infected by M. hyorhinis (24). In 2001, Huang and colleagues conducted a large screening of different cancer tissues using IHC and reported the rates of M. hyorhinis infection that was 40-53% in the lung, breast cancer, esophageal and glioma tissue samples. Atogether, increased mycoplasma infection ratios were detected in gastric carcinoma (56%) compared with other gastric diseases (28-37%, depending on the pathology), and colon carcinoma (55%) in comparison to tissue derived from adenomatous polyps (21%). Importantly, the authors found that M. hyorhinis infection significantly increased in well-differentiated tissues compared with poorly differentiated tissues whereas the most studies report the increased mycoplasma infection in high versus low-grade samples (16).
In 2010, the statistical analysis of Yang’s study indicated that the presence of M. hyorhinis was 64% in gastric cancer tissues and significant relationship was observed among Mycoplasma infection.  By increasing EGFR and ERK1 / 2 phosphorylation, M. hyorhinis can probably promote the migration of tumor cells, invasions, and metastases in vitro and in vivo. The migration of infected cells can be inhibited by an antibody against the M. hyorhinis p37 protein (17).
In 2010, Elisabetta Mariotti et al. reported the cancer cells infected by M. hyorhinis and there was the highest number of CD133+ cells compared to the same cells, whereas they were not effective when exposed to the antibiotic treatment. Their results showed when M. hyorhinis caused infection the percent of CD133 positive cells increased.. Therefore, M. hyorhinis infection plays an important role in the quality of human colon cancer cell lines, leading to false positives in the expression of cancer stem cells, which presents the expression of CD133 (25).
The Mycoplasma infection was compared in prostate biopsies from healthy individuals and BPH patients, patients with elevated PSA levels, high-grade prostatic intraepithelial neoplasy (HGPIN) and prostate cancer. Patients with prostate cancer or HGPIN indicated an increase in seropositivity for M. hominis and M. hyorhinis antibodies compared with individuals suffering from BPH (19, 26-27).
 

Conclusion
The prevalence of M hyorhinis in various tissues leads to cancer progression in patients with cancer. Therefore, it is necessary to pay more attention to this mycoplasma agent in order to control and understand its mechanism.