Lipoteichoic acids from Staphylococcus aureus stimulate proliferation of human non-small-cell lung cancer cells in vitro

Hattar, Katja; Reinert, Christian Philipp; Sibelius, Ulf; Gökyildirim, Mira Y.; Subtil, Florentine S. B.; Wilhelm, Jochen; Eul, Bastian; Dahlem, Gabriele; Grimminger, Friedrich; Seeger, Werner; Grandel, Ulrich

doi:10.1007/s00262-017-1980-4

Cited by 37 publications

(25 citation statements)

References 60 publications

(71 reference statements)

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“…Growing evidence has indicated that bacterial infection is highly associated with certain human malignancies ( 23 ). It has been reported that lipoteichoic acids from S. aureus induce proliferation of two human non-small-cell lung cancer cell lines, A549 and H226 ( 24 ). However, the role of S. aureus infection in ccRCC still remains to be detected.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

et al. 2018

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The present study aimed to identify new key genes as potential biomarkers for the diagnosis, prognosis or targeted therapy of clear cell renal cell carcinoma (ccRCC). Three expression profiles (GSE36895, GSE46699 and GSE71963) were collected from Gene Expression Omnibus. GEO2R was used to identify differentially expressed genes (DEGs) in ccRCC tissues and normal samples. The Database for Annotation, Visualization and Integrated Discovery was utilized for functional and pathway enrichment analysis. STRING v10.5 and Molecular Complex Detection were used for protein-protein interaction (PPI) network construction and module analysis, respectively. Regulation network analyses were performed with the WebGestal tool. UALCAN web-portal was used for expression validation and survival analysis of hub genes in ccRCC patients from The Cancer Genome Atlas (TCGA). A total of 65 up- and 164 downregulated genes were identified as DEGs. DEGs were enriched with functional terms and pathways compactly related to ccRCC pathogenesis. Seventeen hub genes and one significant module were filtered out and selected from the PPI network. The differential expression of hub genes was verified in TCGA patients. Kaplan-Meier plot showed that high mRNA expression of enolase 2 (ENO2) was associated with short overall survival in ccRCC patients (P=0.023). High mRNA expression of cyclin D1 (CCND1) (P<0.001), fms related tyrosine kinase 1 (FLT1) (P=0.004), plasminogen (PLG) (P<0.001) and von Willebrand factor (VWF) (P=0.008) appeared to serve as favorable factors in survival. These findings indicate that the DEGs may be key genes in ccRCC pathogenesis and five genes, including ENO2, CCND1, PLT1, PLG and VWF, may serve as potential prognostic biomarkers in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

et al. 2018

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“…Real-time-reactions were performed as described before [ 64 ]. The mRNA expressions were expressed as –ΔCt value (Ct value gene of interest – Ct value gene of reference gene [PBGD]).…”

Section: Methodsmentioning

confidence: 99%

Targeting CREB-binding protein overrides LPS induced radioresistance in non-small cell lung cancer cell lines

et al. 2018

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Non-small cell lung cancer (NSCLC) has a very poor prognosis even when treated with the best therapies available today often including radiation. NSCLC is frequently complicated by pulmonary infections which appear to impair prognosis as well as therapy, whereby the underlying mechanisms are still not known. It was investigated here, whether the bacterial lipopolysaccharides (LPS) might alter the tumor cell radiosensitivity. LPS were found to induce a radioresistance but solely in cells with an active TLR-4 pathway. Proteome profiling array revealed that LPS combined with irradiation resulted in a strong phosphorylation of cAMP response element-binding protein (CREB). Inhibition of CREB binding protein (CBP) by the specific inhibitor ICG-001 not only abrogated the LPS-induced radioresistance but even led to an increase in radiosensitivity. The sensitization caused by ICG-001 could be attributed to a reduction of DNA double-strand break (DSB) repair.It is shown that in NSCLC cells LPS leads to a CREB dependent radioresistance which is, however, reversible through CBP inhibition by the specific inhibitor ICG-001. These findings indicate that the combined treatment with radiation and CBP inhibition may improve survival of NSCLC patients suffering from pulmonary infections.

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“…Several studies have demonstrated that TLR-2 forms a complex with CD36 following stimulation by S. aureus LTA. LTA actively participates in bacterial invasion of host cells via contact with host cell receptor CD36, TLR-2, and TLR-2/6 and TLR-2/1 heterodimers, leading to host immune response, such as pathogen phagocytosis and cytokine production (4,7,8,10,24,25).…”

Section: Discussionmentioning

confidence: 99%

Tet38 of Staphylococcus aureus Binds to Host Cell Receptor Complex CD36–Toll-Like Receptor 2 and Protects from Teichoic Acid Synthesis Inhibitors Tunicamycin and Congo Red

2019

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Using an affinity column retention assay, we showed that the purified Tet38 membrane transporter of Staphylococcus aureus bound specifically to host cell CD36 and to the complex CD36–Toll-like receptor 2 (TLR-2), but not to TLR-2 alone or TLR-2 and S. aureus lipoteichoic acid (LTA). We tested the effect of LTA on the internalization of S. aureus tet38 mutant QT7 versus RN6390 by A549 epithelial cells. Addition of anti-LTA antibody to the bacteria prior to adding to A549 cells reduced internalization of QT7 2-fold compared to that with nonspecific antibody treatment. QT7 internalized 4- to 6-fold less than RN6390 with or without anti-LTA antibody. These data suggested that Tet38 and LTA were independently involved in the invasion process. The wall teichoic acid (WTA) inhibitor tunicamycin had an 8-fold decrease in activity with overexpression of tet38 and a 2-fold increase in activity in QT7 (tet38). Reserpine (an inhibitor of efflux pumps) reduced the effect of tet38 overexpression on tunicamycin resistance 4-fold. In addition, tet38 affected growth in the presence of LTA inhibitor Congo red, with overexpression increasing growth and deletion of tet38 reducing growth. In conclusion, Tet38 contributes to S. aureus invasion of A549 via direct binding to CD36 of the complex CD36–TLR-2, and LTA independently bound to TLR-2. The reduction of tunicamycin resistance in the presence of reserpine and the survival ability of the tet38 overexpressor in the presence of Congo red suggest that Tet38 can also protect the synthesis of LTA and WTA in S. aureus against their inhibitors, possibly functioning as an efflux pump.

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Lipoteichoic acids from Staphylococcus aureus stimulate proliferation of human non-small-cell lung cancer cells in vitro

Cited by 37 publications

References 60 publications

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Targeting CREB-binding protein overrides LPS induced radioresistance in non-small cell lung cancer cell lines

Tet38 of Staphylococcus aureus Binds to Host Cell Receptor Complex CD36–Toll-Like Receptor 2 and Protects from Teichoic Acid Synthesis Inhibitors Tunicamycin and Congo Red

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