Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Frille, A.
The Role of Erythropoietin and its Receptor in Growth and Survival of non-small cell Lung Cancer cells
[ Diplomarbeit ] Medical University of Graz; 2012. pp. 77
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Olschewski Horst
- Wohlkönig Christoph
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- Abstract:
- Introduction: Patients with lung cancer have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (rHuEpo) and its derivatives have consistently been shown to reduce the need of blood transfusions and increase the hemoglobin level in lung cancer patients with chemotherapy-induced anemia. Over the past decade, there has been continually growing concern from clinical and preclinical studies that Epo and the presence of its receptor (EpoR) on tumor cells is responsible for adverse implications on the patient¿s outcome. The question has been raised what equivocal role do they play in the treatment of chemotherapy-induced anemia in lung cancer patients in terms of promoting tumor growth and inhibiting cell death in favor of tumor progression and reduced survival of the patient. The aim of this study was to investigate the presence and the functionality of EpoR and the implications of Epo upon growth and survival in lung cancer cells. Materials and Methods: By using quantitative RT-PCR, Western Blot, and immunocytochemical staining, three non-small-cell lung cancer (NSCLC) cell lines (A427, A549, NCI-H358) were analyzed for the presence and the functionality of EpoR. After single administration of 100 U/mL Epo, proliferation was assessed via cell counting during three consecutive days under ambient and hypoxic conditions (1% O2). To investigate Epo¿s effects on apoptosis, cells were also treated once with 100 U/mL Epo under ambient conditions, after two days the cytotoxic chemotherapeutic cisplatin was added, and cells with activated caspase-3 were measured via flow cytometry. Results: Here, we demonstrate that all three NSCLC cell lines express EpoR on mRNA and protein level to a different degree, while it was significantly upregulated (2.3-fold) by hypoxia in NCI-H358 cells (P = 0.011). Nevertheless, while Epo-induced activation and signaling of the receptor remained ambiguous in part, Epo did not promote tumor growth or increased protection from apoptosis in these lung cancer cells. Conclusion: Epo and the expression of its receptor in these NSCLC cells does not seem to play a pivotal role in tumor growth and survival, supporting the safety profile of Epo within this experimental model.