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

Hoppe, T; Kraus, D; Novak, N; Probstmeier, R; Frentzen, M; Wenghoefer, M; Jepsen, S; Winter, J

Hoppe, T; Kraus, D; Novak, N; Probstmeier, R; Frentzen, M; Wenghoefer, M; Jepsen, S; Winter, J.

Afiliación

Hoppe T; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
Kraus D; Department of Prosthodontics, Preclinical Education, and Material Science, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
Novak N; Department of Dermatology and Allergy, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Probstmeier R; Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Frentzen M; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
Wenghoefer M; Department of Oral and Maxillofacial Plastic Surgery, University Hospital Bonn, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Jepsen S; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
Winter J; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany. jochen.winter@ukb.uni-bonn.de.

Tumour Biol ; 37(10): 13789-13798, 2016 Oct.

Article en En | MEDLINE | ID: mdl-27481514

RESUMEN

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.

Asunto(s)

Aggregatibacter actinomycetemcomitans/crecimiento & desarrollo; Proliferación Celular/efectos de los fármacos; Defensinas/farmacología; Encía/patología; Neoplasias de Cabeza y Cuello/patología; Neoplasias de la Boca/patología; Porphyromonas gingivalis/crecimiento & desarrollo; Aggregatibacter actinomycetemcomitans/efectos de los fármacos; Secuencia de Aminoácidos; Antiinfecciosos/farmacología; Apoptosis/efectos de los fármacos; Western Blotting; Carcinoma de Células Escamosas/tratamiento farmacológico; Carcinoma de Células Escamosas/genética; Carcinoma de Células Escamosas/microbiología; Carcinoma de Células Escamosas/patología; Estudios de Casos y Controles; Estudios de Seguimiento; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; Encía/efectos de los fármacos; Encía/metabolismo; Encía/microbiología; Neoplasias de Cabeza y Cuello/tratamiento farmacológico; Neoplasias de Cabeza y Cuello/genética; Neoplasias de Cabeza y Cuello/microbiología; Humanos; Técnicas para Inmunoenzimas; Neoplasias de la Boca/tratamiento farmacológico; Neoplasias de la Boca/genética; Neoplasias de la Boca/microbiología; Invasividad Neoplásica; Estadificación de Neoplasias; Porphyromonas gingivalis/efectos de los fármacos; Pronóstico; ARN Mensajero/genética; Reacción en Cadena en Tiempo Real de la Polimerasa; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Homología de Secuencia de Aminoácido; Transducción de Señal/efectos de los fármacos; Células Tumorales Cultivadas

Palabras clave

EGFR signaling; Human defensins; OSCC; Proliferation

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Aggregatibacter actinomycetemcomitans / Porphyromonas gingivalis / Defensinas / Proliferación Celular / Encía / Neoplasias de Cabeza y Cuello Tipo de estudio: Observational_studies / Prognostic_studies Idioma: En Revista: Tumour Biol Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos

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