The Mycoplasma hyorhinis p37 Protein Rapidly Induces Genes in Fibroblasts Associated with Inflammation and Cancer

• Published in: PloS one 2015-10, Vol.10 (10), p.e0140753-e0140753
• Main Authors: Gomersall, Amber Cathie, Phan, Huy Anh, Iacuone, Sylvana, Li, Song Feng, Parish, Roger W
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Arthritis; Bacterial Proteins - genetics; Bacterial Proteins - isolation & purification; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Bonding; Breast cancer; Cancer; Cells, Cultured; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - microbiology; Gastric cancer; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genes; Hydrogen; Hydrogen bonding; Immunoglobulins; Infections; Inflammation; Inflammation - etiology; Interleukin 6; Interleukin-6 - metabolism; Metastases; Metastasis; Mice; Mutagenesis; Mutation; Mycoplasma; Mycoplasma hyorhinis - physiology; Mycoplasma Infections - complications; Mycoplasma Infections - genetics; Mycoplasma Infections - microbiology; Neoplasms - etiology; NIH 3T3 Cells; Ovarian cancer; Prostate; Protein Binding; Proteins; Recombinant Proteins; Science; Signal Transduction - drug effects; Soil sciences; Stat3 protein; STAT3 Transcription Factor - metabolism; Stomach cancer; Thiamine; Thiamine Pyrophosphate - metabolism; Time Factors; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumorigenesis; Tumors; Valine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140753

The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers. Here we show in NIH3T3 fibroblasts, p37 rapidly induces the expression of genes implicated in inflammation and cancer progression. This gene activation was principally via the Tlr4 receptor. Activity was lost from p37 when the C-terminal 20 amino acids were removed or the four amino acids specific for the hydrogen bonding of thiamine pyrophosphate had been replaced by valine. Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression. Since cancer associated fibroblasts support growth, invasion and metastasis via their ability to regulate tumour-related inflammation, the rapid induction in fibroblasts of pro-inflammatory genes by p37 might be expected to influence cancer development.