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Die Rolle von Interleukin-11 beim Osteosarkom

The role of interleukin-11 in osteosarcoma

  • Schwerpunkt: Tumoren des Knochens und der Gelenke
  • Published:
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Zusammenfassung

Das Osteosarkom ist ein meist hochmaligner, mesenchymaler Tumor. Seine Zellen sind definitionsgemäß in der Lage, Osteoid zu bilden, welches zu Tumorknochen ausreifen kann. Osteosarkome bilden häufig hämatogene Metastasen in der Lunge. Die Tumore treten in Europa mit einer Inzidenz von etwa 2 bis 5 Neuerkrankungen pro 1.000.000 Einwohner und Jahr auf. Die Ursachen sind nicht abschließend geklärt, jedoch kann ein Osteosarkom durch eine vorherige Strahlentherapie oder die Exposition mit radioaktiver Strahlung ausgelöst werden. Therapeutisch folgt auf eine neoadjuvante Chemotherapie und eine Operation mit dem Ziel der vollständigen Tumorresektion eine weitere, postoperative Chemotherapie, was zu einer 5‑Jahres-Überlebensrate von etwa 70 % über alle Stadien führt. Untersuchungen der letzten Jahre haben gezeigt, dass die Expression des Oberflächenproteins Interleukin-11-Rezeptor (IL-11R) mit einer schlechten Prognose der Patienten korreliert. Der IL-11R wird von seinem Liganden, dem Zytokin IL-11, aktiviert. IL-11 aktiviert in seinen Zielzellen eine Reihe von Signalwegen und ist als wichtiger Regulator der Knochenhomöostase bekannt. Patienten mit dysfunktionalem IL-11-Signalweg weisen verschiedene Arten der Kraniosynostose auf. Bei Osteosarkomzellen fördert IL-11 die Zellproliferation in vitro. Der IL-11-Signalweg konnte in präklinischen Mausmodellen von primären intratibialen Osteosarkomen zur Reduktion des Tumorwachstums sowie weniger Metastasierung in die Lunge genutzt werden. Dieser Artikel gibt einen Überblick über die Häufigkeit, Klassifikation und Ätiologie des Osteosarkoms und führt in die grundlegende Biologie des Zytokins IL-11 ein. Er beschreibt außerdem die bisherigen Erkenntnisse zur Rolle von IL-11 beim Osteosarkom und zeigt mögliche therapeutische Optionen auf.

Abstract

Osteosarcoma is an often highly malignant mesenchymal tumor. By definition, osteosarcoma cells are able to form osteoid, which can mature into tumor bone. Osteosarcoma metastasizes preferentially to the lung. In Europe, the incidence is between 2 and 5 new diagnoses per 1,000,000 people per year. The underlying mechanisms for osteosarcoma formation are not well understood. However, previous radiotherapy or exposition to nuclear radiation increase the risk of osteosarcoma. Patients are usually treated with a neoadjuvant chemotherapy, followed by complete surgical resection of the tumor and post-surgical chemotherapy, which leads to a five-year survival rate of approximately 70% for all stages. Scientific publications in recent years have shown that expression of the cell surface protein interleukin-11 receptor (IL-11R) correlates with a worse prognosis for patients. The IL-11R is activated by its ligand, the cytokine IL-11. IL-11 activates several intracellular signaling cascades within its target cells and is known to be an important regulator of bone homeostasis. Patients with dysfunctional IL-11 signaling display different forms of craniosynostosis. IL-11 induces proliferation of osteosarcoma cell lines in vitro, and the IL-11 signaling cascade was further used to reduce tumor growth and lung metastasis in preclinical mouse models of primary intratibial osteosarcoma. This article gives a comprehensive overview of the frequency, classification, and etiology of osteosarcoma and describes the basic biology of the cytokine IL-11. Furthermore, it summarizes current knowledge about the functional role of IL-11 in osteosarcoma and lists possible therapeutic opportunities.

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Danksagung

Die Autoren danken den weiteren Mitgliedern der Arbeitsgruppe für Korrekturen und Kommentare zum Manuskript. Weitere Forschung zu IL-11 im Labor von C. Garbers wird von der Deutschen Forschungsgemeinschaft gefördert (Projektnummer 125440785 – SFB 877 TP A10).

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Authors and Affiliations

  1. Institut für Pathologie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, 39120, Magdeburg, Deutschland

    Juliane Lokau, Victor Schoeder &  Christoph Garbers

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  1. Juliane Lokau
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  2. Victor Schoeder
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  3. Christoph Garbers
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Correspondence to Christoph Garbers.

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Interessenkonflikt

C. Garbers hat einen „research grant“ der Firma Corvidia Therapeutics (Waltham, MA, USA) erhalten. J. Lokau und V. Schoeder und geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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A. Roessner, Magdeburg

J. Haybäck, Magdeburg

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Lokau, J., Schoeder, V. & Garbers, C. Die Rolle von Interleukin-11 beim Osteosarkom. Pathologe 41, 163–167 (2020). https://doi.org/10.1007/s00292-020-00756-1

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