Pneumologie 2019; 73(S 01)
DOI: 10.1055/s-0039-1678076
Posterbegehung (P07) – Sektion Pneumologische Onkologie
SCLC, Mesotheliom, Grundlagen
Georg Thieme Verlag KG Stuttgart · New York

Brown adipose tissue impairs chemosensitivity in non-small cell lung cancer cells in the context of cancer cachexia

A Frille
1   Abteilung für Pneumologie, Universitätsklinikum Leipzig, Integriertes Forschungs- und Behandlungszentrum (Ifb) Adipositaserkrankungen, Universitätsmedizin Leipzig
,
H Kuhn
2   Universitätsklinikum Leipzig, Dept. für Innere Medizin, Abt. Pneumologie
,
T Ebert
3   University of Leipzig, Dep. of Endocrinology & Nephrology, IFB Adipositaserkrankungen
,
HJ Seyfarth
2   Universitätsklinikum Leipzig, Dept. für Innere Medizin, Abt. Pneumologie
,
H Wirtz
2   Universitätsklinikum Leipzig, Dept. für Innere Medizin, Abt. Pneumologie
› Author Affiliations
Further Information

Publication History

Publication Date:
19 February 2019 (online)

Also available at
 
 

    Background Lung cancer patients often experience cancer cachexia in the course of their progressive disease. Cancer cachexia is associated with reduced quality of life, tolerance to anticancer therapy and shorter patient survival. Brown adipose tissue (BAT) and its derived adipokines may play a crucial role in the development of cancer cachexia and resistance to chemotherapy in lung cancer patients. We aimed to find out whether BAT-derived supernatants reduce chemosensitivity in non-small cell lung cancer (NSCLC) cells.

    Methods Four NSCLC cell lines (H322, A549, PC9, H1650) were subjected to culture media derived from undifferentiated and differentiated BAT. NSCLC cells were treated with cisplatin, gefitinib or osimertinib for 72 hours, respectively. Supernatants from the white adipose tissue cell line 3 T3-L1 served as a control medium. Short-term effects of chemotherapeutic treatment for each NSCLC cell line cultured with conditioned BAT-medium were investigated in terms of proliferation via the colorimetric MTT assay and apoptosis via the flow cytometric annexin V FITC assay. In addition, BAT-derived supernatants were searched for potentially relevant adipokines via enzyme-linked immunosorbent assay.

    Results All NSCLC cell lines cultured with BAT-derived media showed reduced chemotherapy efficacy as compared to control media. In particular, strongest BAT-specific effects were found in A549 and PC9 cells that were treated with cisplatin or gefitinib and were independent of epidermal growth factor receptor mutational status. Moreover, conditioned BAT media protected A549 and H1650 cells from cisplatin-induced apoptosis.

    In search of relevant factors that are responsible for reduced chemotherapy efficacy in NSCLC cells, we found the BAT-derived adipokines irisin, betatrophin, and fibroblast growth factor 21 to be released into the supernatants of BAT.

    Conclusions BAT-derived supernatants reduce chemosensitivity in NSCLC cells. BAT might induce tumor progression potentially via specific adipokine signaling. BAT-derived adipokines, therefore, might mediate not only cancer cachexia, but also reduced chemotherapy efficacy in NSCLC.


    #