PDF herunterladen
Deutsche Zeitschrift für Onkologie 2013; 45(03): 105-111
DOI: 10.1055/s-0033-1334404
Forschung
© Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

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

Johann Lechner
1   Praxisklinik für Ganzheitliche Zahnheilkunde, Grünwalder Str. 10A, 81547 München
,
Volker von Baehr
2   Institut für Medizinische Diagnostik, Nicolaistr. 22, 12247 Berlin
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
09. Oktober 2013 (online)

   Lizenzen und Reprints

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
 

  • Literatur

  • 1 Appay V, Rowland-Jones SL. RANTES: a versatile and controversial chemokine. Trends Immunol 2001; 22: 83-87
    CrossrefPubMedSuche in Google Scholar
  • 2 Azenshtein E, Luboshits G, Shina S et al The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res 2002; 62(4): 1093-1102
    PubMedSuche in Google Scholar
  • 3 Blaber R et al Selective regulation of ICAM-1 and RANTES gene expression after ICAM-1 ligation on human renal fibroblasts. J Am Soc Nephrol 2003; 14(1): 116-127
    CrossrefPubMedSuche in Google Scholar
  • 4 Bolin LM et al Primary sensory neurons migrate in response to the chemokine RANTES. J Neuroimmunol 1998; 81(1−2): 49-57
    CrossrefPubMedSuche in Google Scholar
  • 5 Bouquot JE, Roberts AM, Person P, Christian J. NICO (neuralgia-inducing cavitational osteonecrosis): osteomyelitis in 224 jawbone samples from patients with facial neuralgia. Oral Surg Oral Med Oral Pathol 1992; 73: 307-319
    Suche in Google Scholar
  • 6 Bouquot JE, Shankland WE II, Margolis M. Through-transmission alveolar ultrasonography (TAU) - new technology for evaluation of bone density and desiccation. Comparison with radiology of 170 biopsied alveolar sites of osteoporotic and ischemic disease. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002; 93.
    PubMedSuche in Google Scholar
  • 7 Bouquot JE. Neuralgia inducing cavitational osteonecrosis (NICO). Oral Surg Oral Med Oral Path 1992; 73: 307
    CrossrefPubMedSuche in Google Scholar
  • 8 Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315(26): 1650-1659
    CrossrefPubMedSuche in Google Scholar
  • 9 Eichbaum C. Breast Cancer Cell-derived Cytokines, Macrophages and Cell Adhesion: Implications for Metastasis. Anticancer Res 2011; 31: 3219-3228
    PubMedSuche in Google Scholar
  • 10 Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY. Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst 2005; 17(1): 51-5
    PubMedSuche in Google Scholar
  • 11 Fessele S. Funktionelle Charakterisierung und in silico-Modellierung LPS-induzierbarer Elemente des RANTES-Promotors in humanen Monocyten. Dissertation Uni-Stuttgart http://elib.uni-stuttgart.de/opus/volltexte/2001/830/
    PubMed
  • 12 Fischer M et al Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue. Int J Cancer 2003; 107(2): 197-201
    CrossrefPubMedSuche in Google Scholar
  • 13 Huber J et al CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab 2008; 93: 3215-3221
    CrossrefPubMedSuche in Google Scholar
  • 14 Karnoub A et al Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449 (7162): 557-563
    CrossrefPubMedSuche in Google Scholar
  • 15 Kintscher U et al Tlymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity mediated insulin resistance. Arterioscler Thromb Vasc Biol 2008; 28: 1304-10
    CrossrefPubMedSuche in Google Scholar
  • 16 Lechner J. Kavitätenbildende Osteolysen des Kieferknochens -Systemisch-ganzheitliche Wirkungen der aseptischen Osteonekrosen „Kieferostitis“ und „NICO“ im Kiefer. München: Eigenverlag; 2011. ISBN: 978−3-931351−19−9.
    Suche in Google Scholar
  • 17 Lechner J, Mayer W. Immune messengers in Neuralgia Inducing Cavitational Osteonecrosis (NICO) in jaw bone and systemic interference. Eur J Integr Med 2010; 2: 71-77
    CrossrefPubMedSuche in Google Scholar
  • 18 Lechner J. NICO − Ist fehlende röntgenologische Evidenz Beweis fehlender klinischer Existenz?. ZWR 2010; 11: 578-592
    Thieme ConnectPubMedSuche in Google Scholar
  • 19 Levy JA. The Unexpected Pleiotropic Activities of RANTES. J Immunol 2009; 182 (7): 3945-3946
    CrossrefPubMedSuche in Google Scholar
  • 20 Luettichau von I. Nelson PJ, Pattison JM et al RANTES chemokine expression in diseased and normal human tissues. Cytokine 1996; 8: 89-98
    CrossrefPubMedSuche in Google Scholar
  • 21 Niwa Y et al Correlation of Tissue and Plasma RANTES Levels with Disease Course in Patients with Breast or Cervical Cancer. Clin Cancer Res 2001; 7: 285
    PubMedSuche in Google Scholar
  • 22 Olefsky J Role of the PPARy Receptor in Muscle & Adipose Tissue Metabolism: Studies of Tissue Specific KO Mice. Metabolic Diseases Drug Discovery World Summit, Keynote Presentations, San Diego 2011.
    PubMed
  • 23 Rathanaswami P et al Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential regulation of RANTES genes by inflammatory cytokines. J Biol Chem 1993; 268: 5834-5839
    PubMedSuche in Google Scholar
  • 24 Robert Koch-Institut Hrsg Krebs in Deutschland 2005/2006. Häufigkeiten und Trends, Berlin 2010 Aktualisiert am: 17.09.10.
    PubMedSuche in Google Scholar
  • 25 Schwartz M Signaling Networks in Normal & Abnormal Energy Homeostasis. Metabolic Diseases Drug Discovery World Summit, Keynote Presentations, San Diego 2011.
    PubMed
  • 26 Stulnig T. Adipositas und die Entzündung des Fettgewebes. J Klin Endokrinol Stoffw 2009; 2 (3): 17-21
    PubMedSuche in Google Scholar
  • 27 Time Magazine The Secret Killer, February 2004.
    PubMed
  • 28 Wilke I, Becker S. Osteonekrose − Pathologische Grundlagen. J Miner Stoffwechs 2007; 14 (1): 3-6
    PubMedSuche in Google Scholar
  • 29 Wirth A. Adipositas - Ätiologie, Folgekrankheiten, Diagnose, Therapie. 3. Aufl Berlin: Springer; 2008
    Suche in Google Scholar
  • 30 Wu H et al T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 2007; 115: 102-38
    PubMedSuche in Google Scholar
  • 31 Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond) 2009; 33: 54-66
    CrossrefPubMedSuche in Google Scholar
  • 32 Zischek C et al Targeted stem cell based RANTES/TK suicide gene-therapy in a murine pancreatic cancer tumour model. Deutsche Gesellschaft für Chirurgie 2009; 38: 3-5
    PubMedSuche in Google Scholar