Bacteria peptidoglycan promoted breast cancer cell invasiveness and adhesiveness by targeting toll-like receptor 2 in the cancer cells

Chronic bacterial infection increased the risk of many solid malignancies and the underlying mechanism is usually ascribed to bacterial-caused inflammation. However, the direct interaction of infectious bacteria with cancer cells has been largely overlooked. We identified that highly metastatic brea...

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Bibliographic Details
Published in:PloS one 2010-05, Vol.5 (5), p.e10850
Main Authors: Xie, Wenjie, Huang, Yafang, Xie, Wenling, Guo, Aimin, Wu, Wei
Format: Article
Language:English
Subjects:
Angiogenesis
Antibiotics
Bacteria
Bacterial infections
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Cancer cells
Cancer metastasis
Cancer research
Cell Adhesion - drug effects
Cell culture
Cell Line, Tumor
Chronic infection
Colorectal cancer
Cytokines
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic - drug effects
Health aspects
Health risks
Humans
Infections
Infectious diseases
Inflammation
Inflammatory bowel disease
Interleukin 6
Interleukin-6 - metabolism
Invasiveness
Ligands
Listeria
Mammals
Mediation
Metastases
Metastasis
Neoplasm Invasiveness
NF-kappa B - metabolism
NF-κB protein
Nonsteroidal anti-inflammatory drugs
Oncology
Oncology/Breast Cancer
Pathogenesis
Pathology
Pathology/Cellular Pathology
Peptidoglycan - pharmacology
Peptidoglycans
Phosphorylation
Prostate cancer
Public health
Real time
Rodents
Signal Transduction - drug effects
Smad3 protein
Smad3 Protein - metabolism
Staphylococcus aureus
Staphylococcus aureus - chemistry
Staphylococcus aureus infections
Stat3 protein
STAT3 Transcription Factor - metabolism
TAK1 protein
TLR2 protein
Toll-Like Receptor 2 - metabolism
Toll-like receptors
Transforming Growth Factor beta - metabolism
Transforming growth factors
Tumorigenesis
Vascular endothelial growth factor
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Summary:Chronic bacterial infection increased the risk of many solid malignancies and the underlying mechanism is usually ascribed to bacterial-caused inflammation. However, the direct interaction of infectious bacteria with cancer cells has been largely overlooked. We identified that highly metastatic breast cancer MDA-MB-231 cells expressed high level of Toll-like receptor 2 (TLR2) in contrast to poorly metastatic breast cancer cells and homogenous untransformed breast cells. TLR2 in MDA-MB-231 cells were actively triggered by peptidoglycan (PGN) from infectious bacterium Staphylococcus aureus (PGN-SA), resulting in the promoted invasiveness and adhesiveness of the cancer cells in vitro. PGN-SA induced phosphorylation of TAK1 and IkappaB in the TLR2-NF-kappaB pathway of the cancer cells and stimulated IL-6 and TGF-beta secretion in MDA-MB-231 cells. All these effects were abrogated by TLR2 blockade. Further investigation showed that the NF-kappaB, STAT3 and Smad3 activities were augmented sequentially in MDA-MB-231 cells after PGN-SA stimulation. Phosphorylation of NF-kappaBp65 was initially increased and then followed by phosphorylation of STAT3 and Smad3 in the delayed 4 or 6 hours. NF-kappaB inhibition attenuated STAT3 and Smad3 activities whereas PGN-SA-stimulated cell culture supernatants reversed these inhibitory effects. Our study indicated that TLR2 activation by infectious bacterial PGN played an important role in breast cancer cell invasiveness and illustrated a new link between infectious bacteria and the cancer cells, suggesting the importance of antibiotic therapy to treat cancer with bacterial infection.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0010850