Phenotyping of Human Melanoma Cells Reveals a Unique Composition of Receptor Targets and a Subpopulation Co-Expressing ErbB4, EPO-R and NGF-RReport as inadecuate




Phenotyping of Human Melanoma Cells Reveals a Unique Composition of Receptor Targets and a Subpopulation Co-Expressing ErbB4, EPO-R and NGF-R - Download this document for free, or read online. Document in PDF available to download.

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-2Rgammanull 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.



Author: Irina Mirkina , Emir Hadzijusufovic , Clemens Krepler, Mario Mikula, Diana Mechtcheriakova, Sabine Strommer, Alexander Stella, Er

Source: http://plos.srce.hr/



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