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Smoking, inflammation and small cell lung cancer: recent developments

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Summary

Small cell lung cancer (SCLC) accounts for 15 % of all lung tumors and represents an invasive neuroendocrine malignancy with poor survival rates. This cancer is highly prevalent in smokers and characterized by inactivation of p53 and retinoblastoma. First in vitro expansion of circulating tumor cells (CTCs) of SCLC patients allowed for investigation of the cell biology of tumor dissemination. In the suggested CTC SCLC model, the primary tumor attracts and educates tumor-promoting and immunosuppressive macrophages which in turn arm CTCs to spread and generate distal lesions. Preexisting inflammatory processes associated with chronic obstructive pulmonary disease (COPD) seem to potentiate the subsequent activity of tumor-associated macrophages (TAM). Activation of signal transducer and activator of transcription 3 (STAT3) and expression of chitinase-3-like 1/YKL-40 in SCLC CTCs seems to be associated with drug resistance. In conclusion, inflammation-associated generation of invasive and chemoresistant CTCs most likely explains the characteristic features of SCLC, namely early dissemination and rapid failure of chemotherapy.

Zusammenfassung

Das kleinzelliges Lungenkarzinom (SCLC) ist für 15 % der Lungenkarzinome verantwortlich und stellt eine aggressiv wachsende und invasive neuroendokrine maligne Erkrankung dar, die mit niedrigen Überlebensarten verbunden ist. Dieses Karzinom weist eine hohe Inzidenz bei Rauchern auf und ist vor allem durch die Inaktivierung von p53 und Retinoblastom-Gen charakterisiert. Die erstmalige in vitro Kultur von zirkulierenden Tumorzellen (CTCs) von SCLC Patienten ermöglichte die Untersuchung der Zellbiologie der Tumordissemination. Bei dem vorgeschlagenen Modell der SCLC CTCs rekrutiert der Tumor Makrophagen mit einem wachstumsfördernden und immunsuppressiven Phänotyp, der wiederum CTCs hervorbringt, die invasiv Fernmetastasen setzen. Bereits bestehende Entzündungsprozesse durch chronische obstruktive pulmonäre Erkrankung (COPD) scheinen die nachfolgende Aktivität der tumorassoziierten Makrophagen (TAM) zu potenzieren. Die Aktivierung von STAT3 und Chitinase-3-like-1/YKL-40 in den CTCs führt wahrscheinlich zur Chemoresistenz. Zusammenfassend führt die mit Entzündungen verbundene Entwicklung invasiver und chemoresistenter CTCs zu den typischen Charakteristika des kleinzelligen Lungenkarzinoms, nämlich früher Metastasierung und frühem Versagen der Chemotherapie und damit verweist dieses Modell des SCLC auf neue therapeutische Angriffspunkte.

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  1. Department of Surgery, Medical University of Vienna, 1090, Vienna, Austria

    Gerhard Hamilton

  2. Ludwig Boltzmann Cluster of Translational Oncology, 1090, Vienna, Austria

    Gerhard Hamilton & Barbara Rath

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Hamilton, G., Rath, B. Smoking, inflammation and small cell lung cancer: recent developments. Wien Med Wochenschr 165, 379–386 (2015). https://doi.org/10.1007/s10354-015-0381-6

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