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Links to Cancer
Several species of mycoplasma are frequently detected in different types of cancer cells. These species are:

M. fermentans

M. genitalium

M. hyorhinis

M. penetrans The majority of these mycoplasma have shown a strong correlation to malignant transformation in mammalian cells in vitro.

Mycoplasma infection and host cell transformation
The presence of mycoplasma was first reported in samples of cancer tissue in the 1960s. Since then there have been several studies trying to find and prove the connection between mycoplasma and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic 2. The first visual sign of infection is when the cells gradually shift from their normal form to sickle shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for a solid support in order to grow and proliferate as well as the normal contact dependent inhibition.

Possible Intra cellular mechanisms of Mycoplasmal Malignant Transformation
Karyotypic changes related to mycoplasma infections Cells infected with mycoplasma for an extended period of time show significant chromosomal abnormalities. These include the addition of chromosomes, the loss of entire chromosomes, partial loss of chromosomes and chromosomal translocation. All of these genetic abnormalities may contribute to the process of malignant transformation. Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes. Proto-oncogenes with increased activity caused by these genetic abnormalities include those encoding c-myc, HRAS and vav. The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by mycoplasma as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known.

Partial reversibility of the malignant transformations
The malignant transformation induced by mycoplasma is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time that reversibility is possible varies greatly; it depends primarily on the mycoplasma involved. In the case of M. fermentans, the transformation is reversible up until around week 11 of infection and starts to become irreversible between week 11 and 18. If the bacteria are killed using antibiotics (i.e. ciprofloxacin or Clarithromycin ) before the irreversible stage, the infected cells should return to normal.

Connections to cancer in vivo and future research
Though mycoplasmas are confirmed to be carcinogenic in vitro, it is not yet confirmed whether mycoplasma might be an actual cause of cancer in vivo. The uncertainties regarding the bacteria’s potential to cause malignancies is mostly due to the fact that the cells used for the studies are most often from immortalized cell lines like the BEAS-2B cells. These are essentially cells on the verge of becoming cancer cells. One big problem with using these cells to confirm carcinogenic properties is that they will transform spontaneously after 32 passagings (when a small number of cells are transferred into a new vessel to extend culture duration). This, and the fact that no malignant transformation has been detected in non-immortalized “normal” cells that have been infected, might be an indication that mycoplasmas accelerates a cell’s progression towards malignancy, rather than actually causing it. No mycoplasma-generated cancer has yet to be documented in in vivo cultures. It might, however, be possible that very long, chronic infections of mycoplasma are able to cause cancer in non-immortalized cells. This is not yet known since non-immortalized cells can only divide for a limited number of times, and therefore it has not been possible to keep culturing them long enough to develop cancer. More research is needed to confirm that mycoplasma infections cause cancer or initiate malignancies in human cells. This might be an important step to treat and prevent cancer.

Types of Cancer associated with mycoplasma
Colon cancer: In a study to understand the effects of mycoplasma contamination on the quality of cultured human colon cancer cells, it was found that there is a positive correlation between the amount of M. hyorhinis present in the sample and the percentage of CD133 positive cells (a glycoprotein with an unknown function). Further tests and analysis are required to determine the exact reason for this phenomenon.

Gastric cancer: There are strong indications that the infection of M. hyorhinis contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.

Lung cancer: Studies on lung cancer have supported the belief that there is more than a coincidental positive correlation between the appearance of Mycoplasma strains in patients and the infection with tumorigenesis. Because this is a such a new area of research, more studies must be performed to further understand the correlation and determine possible preventative steps for lung cancer involving mycoplasma.

Prostate cancer: p37, a protein encoded for by M. hyorhinis, has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and the gene expression of the cells to change, causing them to become a more aggressive phenotype.

Renal Cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mycoplasma sp. compared with the healthy control group. This suggests that mycoplasma may play a role in the development of RCC.