Table 1.
In vitro and in vivo studies indicating malignant potential of mycoplasmas.
| Mycoplasma species | Cell line | Observed effect | Country | Year | Reference |
|---|---|---|---|---|---|
| M. orale | Human diploid cell strain WJ-38 from normal embryo lung | (i) Fragmented chromosomes (ii) High level of breaks and polyploidy |
UK | 1965 | [58] |
|
M. hominis M. fermentans M. orale M. pneumoniae M. salivarium |
BHK2I line of hamster fibroblasts | (i) Cell growth with altered colonial morphology | UK | 1966 | [65] |
| Spiroplasma pirum | Mouse NIH 3T3 cells Monkey kidney CV-1 cells |
(i) Morphological changes of cells (ii) Growth on soft agar and tumors development in athymic and BALB/c mice |
USA | 1986 | [64] |
| M. hyorhinis | Mouse FS9 sarcoma cells | (i) Reduction of invasiveness of transformed cells, approved by using specific monoclonal antibody directed against M. hyorhinis-specific protein p37 | Switzerland | 1990 | [72] |
|
M. fermentans M. penetrans |
Mouse embryo C3H cells | (i) Phenotypic changes of infected cells (ii) Ability to form tumors in animals (iii)High soft agar cloning efficiency |
USA | 1995 | [13] |
|
M. fermentans
M. penetrans |
Mouse embryo C3H cells | (i) Multistage malignant transformation (ii) Induction of H-ras and c-myc oncogenes expression (iii) Morphological changes and uncontrolled cell growth |
USA | 1997 | [67] |
| Acholeplasma laidlawii | Human uterine leiomyosarcoma cell line SK-UT-1B | (i) Chromosomal aberrations (ii) Karyotypic variability |
Russia | 1998 | [60] |
|
M. fermentans M. penetrans M. salivarium M. genitalium M. pneumoniae M. orale M. pirum |
Murine hematopoietic 32D cell line | (i) Activation of NF-Κb transcriptiontranscrption factor (ii) Continuous growth without interleukin stimulation (iii) Chromosomal changes and trisomy 19 |
USA | 1999 | [50] |
|
M. fermentans M. genitalium M. hominis M. penetrans |
Immortalized cervical and prostatic epithelial cells | (i) Alteration in expression of cytokine genes (more profoundly in cervical epithelial cells) - (ii) radually alterationaltereration of important biological properties |
USA | 2000 | [69] |
| M. fermentans | Human peripheral blood mononuclear cells (PBMCs) from healthy blood donors | (i) Karyotype change (ii) Chromosomal loss or gain and translocation |
USA | 2004 | [59] |
| M. fermentans | Mouse embryo C3H cells | (i) Aberrant expression of many oncogenes and tumor repressors at different infection stages | USA | 2006 | [68] |
| M. hyorhinis | Prostate cancer PC-3 and DU145 cell lines | (i) Invasion of cancer cells (ii) Nuclear enlargement (iii) Anaplastic cells (iv) Increase of migratory potential (v) Changes in growth rhythm (vi) Changes in morphology and gene expression |
USA | 2007 | [73] |
| Mycoplasma spp. | Different types of cell lines (mesenchymal, epithelial, and myeloid) Immortalized human bronchial epithelial BEAS-2B cells Lung adenocarcinoma A549 cells |
(i) Cell transformation, proliferation, differentiation, a and apoptosis | USA | 2008 | [61] |
|
M. fermentans
M. arginini M. hominis M. arthritidis |
H1299, MCF-7, HCT116, BJ, REF52, 293 cells | (i) Activation of NF-κB (ii) Inhibition of p53 pathway activity (iii) M. arginini showed the strongest effect among the tested species (iv) Cooperation with some oncogenes in cell transformation |
Russia USA |
2008 | [71] |
|
M. genitalium M. hyorhinis |
Benign human prostate cells (BPH-1) | (i) Malignant transformation (ii) Formation of xenograft tumors in athymic mice (iii) Increase in karyotypic entropy (iv) Accumulation of chromosomal aberrations and polysomy |
USA | 2009 | [62] |
| M. hyorhinis | Human MGC803 gastric carcinoma cells | (i) Elevation of tumor cell migration, invasion, and metastasis | China | 2010 | [75] |
|
M. fermentans
M. hyorhinis |
Immortalized 32D and COS-7 cell lines HeLa and AGS tumor cell lines |
(i) Growth inhibition of immortalized cell lines and tumor cell lines (ii) Compression of the nucleus (iii) Cell genome degradation (iv) Dysregulation of the expression of genes related to proliferation, apoptosis, tumorigenesis, and signaling pathway |
China | 2011 | [70] |
| M. hyorhinis | Gastric cancer cell MGC803 THP-1 cells PMA-induced macrophages Human monocytes isolated from human peripheral blood mononuclear cells (PBMCs) |
(i) Malignant transformation of gastric cancer cells (ii) Activation of the protein complex NLRP3 inflammasome, controlling the maturation of proinflammatory cytokines |
China | 2013 | [76] |
| M. hyorhinis | Gastric cancer cell AGS Gastric cancer cell MGC803 Immortalized human gastric epithelia GES-1 Primary human fetal colon fibroblasts CC-18Co Human umbilical vein endothelial cell (HUVEC) Primary mouse embryonic epithelia (MEF) Primary mouse gastric epithelia (PMGE) |
(i) Promotion of gastric cancer cell invasiveness (ii) Activation of NF-κB pathway |
China | 2014 | [74] |
| Mycoplasma spp. | LM-Mel-14, 24, and 34 cell lines LM-Mel-53, 56, 62, and 93 cell lines de novo established from patient tumors in stem cell media |
(i) Damage and alteration of stem cells properties (clonogenicity, proliferation, and global gene expression) (ii) Expression of putative cancer stem cell markers |
Australia USA |
2016 | [66] |
| M. fermentans | Colon carcinoma HCT116 cell line Female NOD/SCID and NOD/SCID-γ (NSG) mice |
(i) Lymphomagenesis in SCID mice (ii) Decrease in the activity of proteins involved in cellular pathways required for DNA repair (iii) Impair of anticancer functions (iv) Reduction of anticancer drugs efficacy (v) M. fermentans chaperone protein DnaK (heath shock protein) was proved to cause these oncogenetic properties |
USA | 2018 | [79] |
| M. hyorhinis | Human lung mucoepidermoid carcinoma NCI-Н292 cells | (i) Decrease of sensitivity of tumerous cells to anticancer (nutlin-3) (ii) Infected cells were more capable of growing and dividing |
Russia | 2018 | [80] |
| Mycoplasma spp. | Dopaminergic neuronal BE-M17 cell line | (i) Induction of oxidative stress with no inflammatory response (ii) DNA damage (iii) Decrease in the efficiency of pathways necessary for DNA repair |
USA | 2019 | [63] |
| M. hyorhinis | Human gastric cancer MGC803 and BGC823 cell lines | (i) Accumulation of nuclear signaling pathway β‐catenin Enhancement of the expression of downstream β‐catenin genes (ii) Induction of gastric cancer cell motility |
China | 2019 | [77] |
| M. fermentans | HCT116 cells transfected with expression vector containing M. fermentans DnaK | (i) DnaK protein plays a critical role in pathways involved in recognition of DNA damage and repair (ii) Reduction of p53 stability and anticancer functions |
USA | 2020 | [78] |
| Mycoplasma spp. | Chronic myeloid leukemia (CML) K562 and KCL-22 cell lines Macrophages Natural killer |
(i) Cancerous tissues infected by mycoplasmas were protected by macrophages from the attack of natural killer | Singapore Taiwan |
2020 | [81] |