Phenotyping of human melanoma cells reveals a unique composition of receptor targets and a subpopulation co-expressing ErbB4, EPO-R and NGF-R.
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.
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
Irina
I
Mirkina
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Division of Hematology & Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria ; Department/Clinic for Companion Animals and Horses, Clinic for Small Animals, Clinical Unit of Internal Medicine, University of Veterinary Medicine Vienna, Austria.
Emir
E
Hadzijusufovic
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Clemens
C
Krepler
Department of Dermatology, Medical University of Vienna, Vienna, Austria ; Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
Mario
M
Mikula
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Department of Pathophysiology & Allergy Research, Medical University of Vienna, Vienna, Austria.
Diana
D
Mechtcheriakova
Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
Sabine
S
Strommer
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Alexander
A
Stella
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Department of Pathophysiology & Allergy Research, Medical University of Vienna, Vienna, Austria ; Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine, Medical University of Vienna and University Vienna, Vienna, Austria.
Erika
E
Jensen-Jarolim
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Christoph
C
Höller
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Volker
V
Wacheck
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Hubert
H
Pehamberger
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria ; Division of Hematology & Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Peter
P
Valent
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D009368:Neoplasm Transplantation; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics; D066247:Receptor, ErbB-4; D020800:Receptor, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D020800:Receptor, Nerve Growth Factor; D017467:Receptors, Erythropoietin; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D066247:Receptor, ErbB-4