title: Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins.
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.
authors.affiliation: Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hoppe
authors.affiliation: Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kraus
authors.affiliation: Department of Dermatology and Allergy, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Novak
authors.affiliation: Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Probstmeier
authors.affiliation: Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Frentzen
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wenghoefer
authors.affiliation: Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jepsen
authors.affiliation: Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany. jochen.winter@ukb.uni-bonn.de.
authors.forename: J
authors.initials: J
authors.lastname: Winter
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects / Q000254:growth & development*; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D023082:Defensins / Q000494:pharmacology*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000254:growth & development*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000890:Anti-Infective Agents; D023082:Defensins; D012333:RNA, Messenger
keywords: EGFR signaling; Human defensins; OSCC; Proliferation