Phenotyping of human melanoma cells reveals a unique composition of receptor targets and a subpopulation co-expressing ErbB4, EPO-R and NGF-R

• Published in: PloS one Vol. 9; no. 1; p. e84417
• Main Authors: Mirkina, Irina, Hadzijusufovic, Emir, Krepler, Clemens, Mikula, Mario, Mechtcheriakova, Diana, Strommer, Sabine, Stella, Alexander, Jensen-Jarolim, Erika, Höller, Christoph, Wacheck, Volker, Pehamberger, Hubert, Valent, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.01.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antigen (tumor-associated); Antigens; Antigens, CD - genetics; Antigens, CD - metabolism; B cells; Biology; Biotechnology; Boltzmann, Ludwig Eduard (1844-1906); Cancer metastasis; Cancer therapies; CD20 antigen; CD44 antigen; CD45 antigen; CD63 antigen; Cell Line, Tumor; Cell surface; Comparative analysis; Cytokine receptors; Cytokines; Cytometry; Dermatology; Disease; Drugs; ErbB-2 protein; ErbB-3 protein; Erythropoietin; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genetic transformation; Growth factors; Hematology; Humans; Immunophenotyping; Insulin-like growth factor I; Intercellular adhesion molecule 1; Interleukin 2 receptors; Kinases; Lesions; Male; MDR1 protein; Medical prognosis; Medicine; Melanocytes; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Metastases; Metastasis; Mice; Mice, Inbred NOD; Neoplasm Transplantation; Nerve growth factor; Oncology; Patients; PD-1 protein; Phenotyping; Prognosis; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Proto-Oncogene Proteins c-kit - deficiency; Proto-Oncogene Proteins c-kit - genetics; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-4; Receptor, Nerve Growth Factor - genetics; Receptor, Nerve Growth Factor - metabolism; Receptors; Receptors, Erythropoietin - genetics; Receptors, Erythropoietin - metabolism; Skin; Skin cancer; Skin diseases; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Stem cells; Studies; Subpopulations; Transformation; Veterinary medicine; Austria
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084417

Malignant melanoma is a life-threatening skin cancer increasingly diagnosed in the western world. In advanced disease the prognosis is grave. Growth and metastasis formation in melanomas are regulated by a network of cytokines, cytokine-receptors, and adhesion molecules. However, little is known about surface antigens and target expression profiles in human melanomas. We examined the cell surface antigen profile of human skin melanoma cells by multicolor flow cytometry, and compared their phenotype with 4 melanoma cell lines (A375, 607B, Mel-Juso, SK-Mel28). Melanoma cells were defined as CD45-/CD31- cells co-expressing one or more melanoma-related antigens (CD63, CD146, CD166). In most patients, melanoma cells exhibited ErbB3/Her3, CD44/Pgp-1, ICAM-1/CD54 and IGF-1-R/CD221, but did not express CD20, ErbB2/Her2, KIT/CD117, AC133/CD133 or MDR-1/CD243. Melanoma cell lines were found to display a similar phenotype. In most patients, a distinct subpopulation of melanoma cells (4-40%) expressed the erythropoietin receptor (EPO-R) and ErbB4 together with PD-1 and NGF-R/CD271. Both the EPO-R+ and EPO-R- subpopulations produced melanoma lesions in NOD/SCID IL-2Rgamma(null) (NSG) mice in first and secondary recipients. Normal skin melanocytes did not express ErbB4 or EPO-R, but expressed a functional KIT receptor (CD117) as well as NGF-R, ErbB3/Her3, IGF-1-R and CD44. In conclusion, melanoma cells display a unique composition of surface target antigens and cytokine receptors. Malignant transformation of melanomas is accompanied by loss of KIT and acquisition of EPO-R and ErbB4, both of which are co-expressed with NGF-R and PD-1 in distinct subfractions of melanoma cells. However, expression of EPO-R/ErbB4/PD-1 is not indicative of a selective melanoma-initiating potential.