No erythropoietin-induced growth is observed in non-small cell lung cancer cells

  • Authors:
    • Armin Frille
    • Katharina Leithner
    • Andrea Olschewski
    • Horst Olschewski
    • Christoph Wohlkönig
    • Andelko Hrzenjak
  • View Affiliations

  • Published online on: December 12, 2017     https://doi.org/10.3892/ijo.2017.4225
  • Pages:518-526
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Abstract

Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death. The question has been raised whether Epo promotes tumor growth and inhibits the death of cancer cells. In this study, we investigated the presence and functionality of EpoR, as well as the implications of Epo upon the proliferation and survival of lung cancer cells. Since the protein expression of both Epo and EpoR is induced by hypoxia, which is frequently present in lung cancer, the cells were treated with Epo under both normoxic and hypoxic conditions (1% O2). By using quantitative (real-time) PCR, western blot analysis, and immunocytochemical staining, three non-small cell lung cancer (NSCLC) cell lines (A427, A549 and NCI-H358) were analyzed for the expression of EpoR and its specific downstream signaling pathways [Janus kinase 2 (Jak2)-signal transducer and activator of transcription 5 (STAT5), phosphatidylinositol-3-kinase (PI3K)-Akt, mitogen-activated protein (MAP) kinase]. The effects of 100 U/ml Epo on cell proliferation and cisplatin-induced apoptosis were assessed. All NSCLC cell lines expressed EpoR mRNA and protein, while these levels differed considerably between the cell lines. We found the constitutive phosphorylation of EpoR and most of its downstream signaling pathways (STAT5, Akt and ERK1/2) independently of Epo administration. While Epo markedly enhanced the proliferation and reduced apoptosis of Epo-dependent UT-7/Epo leukemia cells, it did not affect tumor cell proliferation or the cisplatin-induced apoptosis of NSCLC cells. Thus, this in vitro study suggests that there are no tumor-promoting effects of Epo in the NSCLC cell lines studied, neither under normoxic nor under hypoxic conditions.

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February 2018
Volume 52 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
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APA
Frille, A., Leithner, K., Olschewski, A., Olschewski, H., Wohlkönig, C., & Hrzenjak, A. (2018). No erythropoietin-induced growth is observed in non-small cell lung cancer cells. International Journal of Oncology, 52, 518-526. https://doi.org/10.3892/ijo.2017.4225
MLA
Frille, A., Leithner, K., Olschewski, A., Olschewski, H., Wohlkönig, C., Hrzenjak, A."No erythropoietin-induced growth is observed in non-small cell lung cancer cells". International Journal of Oncology 52.2 (2018): 518-526.
Chicago
Frille, A., Leithner, K., Olschewski, A., Olschewski, H., Wohlkönig, C., Hrzenjak, A."No erythropoietin-induced growth is observed in non-small cell lung cancer cells". International Journal of Oncology 52, no. 2 (2018): 518-526. https://doi.org/10.3892/ijo.2017.4225