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
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
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.
PLoS One. 2014 Jan 29;9(1):e84417. doi: 10.1371/journal.pone.0084417. eCollection 2014.
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.
恶性黑色素瘤是一种在西方世界诊断率日益增加的危及生命的皮肤癌。在疾病晚期，预后严峻。黑色素瘤的生长和转移形成受细胞因子、细胞因子受体和黏附分子网络的调节。然而，对于人类黑色素瘤中的表面抗原和靶标表达谱了解甚少。我们通过多色流式细胞术检测了人类皮肤黑色素瘤细胞的细胞表面抗原谱，并将它们的表型与4种黑色素瘤细胞系（A375、607B、Mel-Juso、SK-Mel28）进行比较。黑色素瘤细胞被定义为共表达一种或多种黑色素瘤相关抗原（CD63、CD146、CD166）的CD45-/CD31-细胞。在大多数患者中，黑色素瘤细胞表现出ErbB3/Her3、CD44/Pgp-1、ICAM-1/CD54和IGF-1-R/CD221，但不表达CD20、ErbB2/Her2、KIT/CD117、AC133/CD133或MDR-1/CD243。发现黑色素瘤细胞系表现出相似的表型。在大多数患者中，一个独特的黑色素瘤细胞亚群（4%-40%）共表达促红细胞生成素受体（EPO-R）和ErbB4以及PD-1和NGF-R/CD271。EPO-R+和EPO-R-亚群在初次和二次受体的NOD/SCID IL-2Rγ(null)（NSG）小鼠中均产生黑色素瘤病变。正常皮肤黑素细胞不表达ErbB4或EPO-R，但表达功能性KIT受体（CD117）以及NGF-R、ErbB3/Her3、IGF-1-R和CD44。总之，黑色素瘤细胞表现出独特的表面靶抗原和细胞因子受体组成。黑色素瘤的恶性转化伴随着KIT的缺失以及EPO-R和ErbB4的获得，二者在黑色素瘤细胞的不同亚组分中均与NGF-R和PD-1共表达。然而，EPO-R/ErbB4/PD-1的表达并不表明具有选择性的黑色素瘤起始潜能。
