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Deutsche Zeitschrift für Onkologie 2017; 49(01): 20-27
DOI: 10.1055/s-0043-101090
Forschung
© Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

Onkogenes Schlüsselsignal RANTES/CCL5 – „Cytokine Cross Talk“ des Tumors und „Silent Inflammation“ des Kieferknochens

Oncogenetic Key Signal RANTES/CCL5 – „Cytokine Cross Talk“ in Tumors and Silent Inflammation of Jawbone
Johann Lechner
1   Praxisklinik Ganzheitliche ZahnMedizin, München
,
Volker von Baehr
2   Abteilung für Immunologie und Allergologie im Institut für Medizinische Diagnostik (IMD), Berlin. www.imd-berlin.de
› Author Affiliations
Further Information

Publication History

Publication Date:
02 May 2017 (online)

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Zusammenfassung

Hintergrund Trotz erheblicher therapeutischer Fortschritte sind die meisten malignen Erkrankungen unheilbar geblieben. Gleichzeitig nimmt die Bedeutung der Mikroumgebung, die die Tumorzellen mit „Silent Inflammation“ umgibt, zu. Zielsetzung: Um den Verdacht auf tumorrelevante inflammatorischen Zytokin-Quellen in fettig-degenerativ veränderten Osteolysen/Osteonekrosen des Kieferknochens (FDOK) zu überprüfen, untersuchen wir diese auffällig veränderten Areale auf Zytokin-Muster.

Material und Methoden Bei insgesamt 38 Tumorpatienten untersuchen wir Gewebeproben aus FDOK auf ihren Gehalt an Zytokinen mittels bead-basierter Luminex®-Analyse.

Ergebnisse Auffallend ist der isoliert hohe Gehalt an Chemokin RANTES/CCL5 (R/C) in allen FDOK-Gewebeproben. Ein Fall zeichnet sich durch hohe R/C-Spiegel in der FDOK-Probe und gleichzeitigen Metastasen eines Adenokarzinoms der Brust (MaCa) aus. Die R/C Expression in den 38 FDOK-Proben der Tumorpatienten liegt im Mittel beim 35-fachen gegenüber gesundem Kieferknochen.

Diskussion R/C greift auf mehreren Stufen in Immunreaktionen ein und wird in der wissenschaftlichen Literatur bei vielen Tumoren und insbesondere bei MaCa und dessen Metastasierung als pathogenetische Schlüsselstelle angesehen. R/C ist damit an onkogenen Entwicklungen beteiligt.

Schlussfolgerung Die Autoren schließen aus den Daten der FDOK-Analyse, dass diese Areale hyperaktivierte Signaltransduktionskaskaden des Chemokins R/C exprimieren, die pathogenetische Autoimmunprozesse bei vielen Tumoren und insbesondere beim MaCa und dessen Metastasierung induzieren können. Verbindet man die in der Literatur dargestellte R/C- und CCR5-Signalinduktion bei Tumoren und die von uns erhobenen Daten, kann vorgeschlagen werden, FDOK in ein integratives Therapiekonzept bei Tumoren und möglicherweise auch bei MaCa einzubeziehen.

ABSTRACT

Background Despite significant therapeutic advances most malignancies, as well as adenocarcinomas of the breast, remained incurable. At the same time, the importance of the microenvironment surrounding the tumor cells with “silent inflammation” increases.

Objective To check the suspected tumor-relevant inflammatory cytokine sources in fatty-degenerative osteonecrotic jawbone (FDOJ), we analyze these conspicuously altered jawbone areas to assess the expression and quantification of cytokine expression.

Material and Method In 38 tumor patients we determine the levels of cytokines by bead-based Luminex® analysis in samples of FDOJ.

Results Striking is the high content of chemokine RANTES/CCL5 (R/C) in all 38 tissue samples. A single case is characterized by high R/C levels in FDOJ sample and simultaneously by metastasizing cells inside the FDOJ sample. The R/C expression in all 38 FDOJ samples is on average at 35 fold higher compared to healthy jawbone.

Discussion R/C interacts on several levels in immune responses and is considered in scientific literature as pathogenetic key point in tumor growth. The study supports a potential mechanism where FDOJ is a mediating link specifically in breast cancer (MaCa) and its metastasis. R/C is thus involved intensively in oncogenic propulsion progress developments.

Conclusion The authors conclude from the data of FDOJ analysis that these areas express hyperactivated signal transduction of the chemokine R/C, induce pathogenetic autoimmune processes in tumors, MaCa and its metastasis and serve as a possible cause. Combining the R/C signal induction of tumors and the information we collect illustrated, it may be suggested to involve FDOJ in an integrative therapy concept for tumor therapy.

Schlüsselwörter

Chemokin RANTES/CCL5 - Tumor-Mikroumgebung - Osteolysen des Kieferknochens - Brustkrebs - Metastasen - Multiplex-Analyse - Signalweg-Überexpression - Cytokine Cross-Talk

Key words

chemokine RANTES/CCL5 - osteonecrosis in jawbone - tumor microenvironment - bead based Luminex® analysis - hyperactivated signaling pathways - cytokine cross-talk
 

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