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Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins

  • Original Article
  • Published:
Tumor Biology

Abstract

The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.

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Abbreviations

AKT:

RAC-alpha serine/threonine-protein kinase

DMEM:

Dulbecco’s modified Eagle’s medium

ERK1/2:

Extracellular signal-regulated kinases 1/2

FCS:

Fetal calf serum

Gab1:

GRB2-associated binding protein 1

NF-κB:

Nuclear factor “kappa-light-chain-enhancer” of activated B cells

SHC:

SHC-transforming protein

TLR:

Toll-like receptors

Tyr:

Tyrosine

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Acknowledgments

The authors are grateful to D. Lalaouni and I. Beier for their technical assistance. TH, NN, MW, SJ, and JW were supported by a grant of the German Research Foundation (KFO 208; TH (TP9/10), NN (TP1), SJ (TP2), MW, and JW (TP10)) and the Medical Faculty of the University of Bonn.

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Authors and Affiliations

  1. Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany

    T. Hoppe, M. Frentzen, S. Jepsen & J. Winter

  2. Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany

    D. Kraus

  3. Department of Dermatology and Allergy, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    N. Novak

  4. Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    R. Probstmeier

  5. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    M. Wenghoefer

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  1. T. Hoppe
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  2. D. Kraus
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Correspondence to J. Winter.

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T. Hoppe and D. Kraus contributed equally to this work.

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Hoppe, T., Kraus, D., Novak, N. et al. Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins. Tumor Biol. 37, 13789–13798 (2016). https://doi.org/10.1007/s13277-016-5281-x

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  • DOI: https://doi.org/10.1007/s13277-016-5281-x

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