Role of Erythropoietin Receptor Expression in Malignant Melanoma

• Published in: Journal of investigative dermatology Vol. 130; no. 1; pp. 201 - 210
• Main Authors: Mirmohammadsadegh, Alireza, Marini, Alessandra, Gustrau, Annett, Delia, Dana, Nambiar, Sandeep, Hassan, Mohamed, Hengge, Ulrich R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2010; Nature Publishing Group; Elsevier Limited
• Subjects: Anemia - drug therapy; Anemia - etiology; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Biopsy; Cell Movement - drug effects; Cells, Cultured; Dermatology; Erythropoietin - pharmacology; Humans; Janus Kinase 2 - metabolism; Medical sciences; Melanocytes - cytology; Melanocytes - physiology; Melanoma - complications; Melanoma - physiopathology; Melanoma - secondary; Mitogen-Activated Protein Kinase 3 - metabolism; Phosphorylation - drug effects; Phosphorylation - physiology; Receptors, Erythropoietin - genetics; Receptors, Erythropoietin - metabolism; Recombinant Proteins; Signal Transduction - physiology; Skin Neoplasms - complications; Skin Neoplasms - pathology; Skin Neoplasms - physiopathology; STAT3 Transcription Factor - metabolism; Tumors of the skin and soft tissue. Premalignant lesions; Malignant tumor; Erythropoietin; Polypeptide; Dermatology; Malignant melanoma; Cancer
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2009.162

Recombinant human erythropoietin (Epo) is used to prevent and treat tumor-related anemia and improve quality of life in cancer patients. Recent evidence suggested that Epo may adversely affect the survival of selected cancer patients by promoting tumor growth, inhibition of apoptosis, and induction of migration. Epo unfolds its effect on the Epo receptor (EpoR). We show—to the best of our knowledge for the first time—significantly increased EpoR expression in clinical melanoma metastases and primary melanomas in comparison with different sets of nevi by quantitative real-time reverse transcriptase-PCR, immunohistochemistry, and western blot analysis. When assessing the functionality of the EpoR-signaling pathway, recombinant human Epo led to the phosphorylation of JAK-2, signal transducers and activators of transcription 3 (STAT3), and ERK1/2 in several of the melanoma cell lines that were analyzed. Besides, Epo counteracted cisplatin-induced cell death in BLM and MV3 cells. Finally, Epo promoted cell migration of MV3 cells, whereas inhibition of the JAK/STAT and ERK1/2 pathways reduced Epo-mediated migration. In summary, we show the overexpression of functional EpoR expression in about half of the analyzed clinical melanoma metastasis specimens and show anti-apoptotic as well as pro-migratory effects of Epo, which is of importance for the treatment of anemia in advanced melanoma.