Pneumologie 2016; 70 - P21
DOI: 10.1055/s-0036-1584624

Erythropoietin exhibit angiogenic potential and the role of erythropoietin receptor in lung cancer cells

X Liu 1, R Kiefl 1, RM Huber 1
  • 1Medizinische Klinik V, Ludwig-Maximilians Universität München, München

Background: Recombinant human erythropoietins (rHuEPOs), a hormone regulating proliferation and differentiation of erythroid cells is one of the prescription drugs to treat cancer associate anemia. However, rHuEPOs administration to lung cancer patients has been reported to associate with decreased survival, and the mechanism remains controversial.

Objectives:

  • To investigation the angiogenic effect of EPO on human vascular endothelial cells in an in vitro 3D cell culture model.

  • The expression of EPO-Receptor in lung cancer cells including EGFR (epidermal growth factor receptor) wild type/EGFR gene mutation cell lines and whether EPO treatment modifies lung cancer cells growth.

Methods: EPO-Receptor expression in lung cancer cell lines H838, H1650, H1975, HCC827 and small cell lung cancer cell H1339 were measured by ELISA. The cells proliferations were monitored by a real-time cell monitor technology icelligence system in the presence of PBS or EPO for seven days. Vascular endothelial cells HUVEC tube formation assay in EPO or PBS treatment groups were performed in a 3D collagen gel cell culture model.

Results: EPO-Receptor can be detected in EGFR wild type lung cancer cell line H838, and small-cell-lung-cancer cell line H1339 while in EGFR gene mutation lung cancer cell lines H1650, H1975 and HCC827 were not measurable. Although EPO-Receptor was expressed in H838 and H1339, rHuEPOα treatment did not alter the cells proliferation in vitro. However, rHuEPOα significantly promoted HUVEC tube formation in a 3D culture model in vitro.

Conclusion and Outlook: EPO-R is not necessary for lung cancer cells proliferation in vitro. The role of EPO is beyond erythropoiesis, it can be as a strong angiogenesis as well, an animal model will be established in the future. EPO-R may co-expression with EGFR, EPO-R mutation or chimeric receptor between EGFR and EPO-R could be further investigated in the mechanism of EGFR-TKI (tyrosine kinase inhibitors) resistant on the possibility of cross-talk signaling pathway.