8- resp. 7.6-fold) of TRP-2 in the hypoxia treated samples compared to untreated control cells, supporting the observed correlation of Hif-1α expression and the the presence of TRP-2−/Mib-1+ cells. As previously shown [17], Dct expression in the hair follicle bulge labels

melanocyte stem cells. Fluorescence labelling of Trp-2 (Dct) showed positivity for Dct in the melanocytes in the hair bulb region, thereby showing that Trp-2 expression is not restricted to the stem cell compartment (Figure 3D). BGB324 nmr These findings show that TRP-2 is a melanocytic differentiation antigen and not a stem cell marker. In this study, we characterize TRP2 as a melanoma differentiation antigen without evidence to be a stem cell marker. Our data are consistent with a model that an aggressive proliferative TRP-2-negative subpopulation exists in primary melanoma, which significantly increases with tumor progression. In the past years a major effort was to define new tumor targets for immunotherapeutic purposes. Ideally these targets should be stably and specifically expressed in the tumor and able to trigger an immune response. TRP-2 Gefitinib cell line is an immunogenic enzyme involved in the melanin synthesis

and considered as a melanoma differentiation marker but also as a melanocyte stem cell marker. There is evidence that cancer stem cells are involved in the tumor progression and dissemination, which includes a series of distinct steps that together comprise the “invasion–metastasis cascade” [22]. Therefore, a therapy PAK6 that targets cancer stem cells could be highly effective

if not curative. Accordingly, the role of TRP-2 in melanoma as a stem cell or differentiation marker is a relevant issue for therapeutical purposes. In mice, we show that Trp2 (Dct) is a differentiation antigen and not a stem cell marker demonstrated by the fact that the population of melanoblasts/melanocytes express Trp-2 as well as melanocyte stem cells, located in the bulge region of the hair follicle (Figure 3D-F). In order to study the expression of TRP-2 (DCT) in humans, we analysed primary and metastatic melanomas as well as patients’ derived primary melanoma cell cultures. We could demonstrate that TRP-2 expression is significantly correlated with expression of the melanoma differentiation antigen Melan A in primary melanomas, and melanoma metastases. These data suggest that TRP-2 expression is rather correlated with the differentiation degree of melanocytes as indicated by the co-expression with Melan A. In addition, there is a significant loss of TRP-2 expression with tumor progression. These results underline that TRP-2 is a differentiation antigen and not a stem cell marker also in human melanoma. From molecular profiling studies it is established that progression of tumors, including malignant melanomas, is associated with an accumulation of new genetic hits [23]. It is therefore reasonable that differentiation antigens are lost with tumor progression.