Hyperaktivierte Signaltransduktionskaskaden des Chemokins RANTES/CCL5 in Osteopathien des Kieferknochens beim Mammakarzinom

Zusammenfassung

Gewebeproben aus fettig-degenerativ osteolytischen Kieferknochen Spongiosa/NICO wurden auf ihren Gehalt an Zytokinen mittels bead-basierter Luminex^®-Analyse untersucht. Auffallend war der isoliert hohe Gehalt an Chemokin RANTES/CCL5 in allen 31 NICO-Gewebeproben. Die Zytokin-Analysen des Kieferknochen-/NICO-Areals eines Falles mit Metastasen eines Adenokarzinoms der Brust und eines zweiten Mammakarzinom- (MaCa-)Falles werden mit den Zytokinprofilen von 7 MaCa-Patientinnen verglichen sowie mit zwei in der Literatur zu findenden RANTES-Werten in Brustkrebsgewebe selbst. Die RANTES-Expression im NICO-Gewebe liegt im Mittel beim 5-fachen gegenüber Vergleichswerten aus pathologischen Gewebewerten von Brustkrebskollektiven. RANTES greift auf mehreren Stufen in Immunreaktionen ein und wird in der wissenschaftlichen Literatur bei Brustkrebs und bei dessen Metastasierung als pathogenetische Schlüsselstelle angesehen und ist damit an onkogenen Entwicklungen beteiligt. Die Autoren schließen aus den Daten der NICO-Analyse, dass NICO als lokale krankhafte Gewebebildung im Kieferknochen existiert und dass hyperaktivierte Signaltransduktionskaskaden des Chemokins RANTES/CCL5 eine pathogenetische Induktion von Autoimmunprozessen auslösen können. Die Zusammenhänge mit MaCa und dessen Metastasierung lassen die Anregung zu, die fettigen Osteolysen des Kieferknoches in ein integratives Therapiekonzept bei MaCa einzubeziehen.

Summary

Background: Jawbone cavitations (JC) are hollow dead spaces in jaw bone with dying or dead bone marrow. These areas are defined as fatty degenerative osteonecrosis of jawbone or „Neuralgia Inducing Cavitational Osteonecrosis/NICO“ and may produce facial pain. They have been linked with the immune system and chronic illnesses. Little is known about the underlying cause\effect relationship. Objectives: JC bone samples were analyzed to assess the expression and quantification of immune modulators which can play a role in the pathogenesis of BC. The study supports a potential mechanism where JC is a mediating link in BC. Material and Methods: Samples of fatty softened bone taken from JC have been extracted from 31 patients with systemic diseases and from three patients with normal JB. The specimens were analyzed by bead-based multiplex technology and tested for 7 immune messengers. Results: RANTES and FGF-2 are found at overexpressed levels in the JC tested. Other cytokines could not be detected at exceeding levels. Discussion: The study confirms that JC is able to produce inflammatory messengers, primarily RANTES. RANTES is implicated in BC and BC metastasis. The exceeding levels of RANTES in eight BC patients are compared to levels published in medical journals. Levels detected in JC are fivefold higher than in BC tissue. Two cases with BC are demonstrated including the diagnostic problems of JC. Conclusion: The study suggests that JC might serve as a possible cause of BC, through RANTES that they produce. Thus JC and the implicated immune messenger RANTES give an integrative aspect of BC. Surgical debridement of JC may be a key to reversing BC. There is the need to raise awareness of JC throughout medicine and dentistry.

Schlüsselwörter

Chemokin RANTES/CCL5 - Osteopathien des Kieferknochens - bead- basierte Luminex^®-Analyse - Mammakarzinom - Metastasierung - hyperaktivierte Signaltransduktionskaskaden

Keywords

Chemokine RANTES/CCL5 - breast cancer - jaw bone cavitations - bead based Luminex^® analysis - metastasis - hyperactivited signaling transduction cascades

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