Pneumologie 2019; 73(03): 189
DOI: 10.1055/s-0038-1676413
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

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

A Frille
1   Department of Respiratory Medicine, University of Leipzig, Leipzig
2   Integrated Treatment and Research Centre (IFB) AdiposityDiseases, Leipzig University Medical Centre, Leipzig
,
H Kuhn
1   Department of Respiratory Medicine, University of Leipzig, Leipzig
,
T Ebert
2   Integrated Treatment and Research Centre (IFB) AdiposityDiseases, Leipzig University Medical Centre, Leipzig
3   Department of Endocrinology and Nephrology, University of Leipzig, Leipzig
,
HJ Seyfarth
1   Department of Respiratory Medicine, University of Leipzig, Leipzig
,
H Wirtz
1   Department of Respiratory Medicine, University of Leipzig, Leipzig
› Author Affiliations
Further Information

Publication History

Publication Date:
12 March 2019 (online)

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    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 3T3-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 that were 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.


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