An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative

作者：Lenggenhager Daniela; Curioni Fontecedro Alessandra; Storz Martina; Shakhova Olga; Sommer Lukas; Widmer Daniel S; Seifert Burkhardt; Moch Holger; Dummer Reinhard; Mihic Probst Daniela^*

来源：Translational Oncology, 2014, 7(2): 206-212.

DOI：10.1016/j.tranon.2014.02.018

Despite existing vaccination strategies targeting TRP-2, its function is not yet fully understood. TRP-2 is an enzyme involved in melanin biosynthesis and therefore discussed as a differentiation antigen. However, in mice Trp-2 was shown to be expressed in melanocyte stem cells of the hair follicle and therefore also considered as an indicator of stemness. A proper understanding of the TRP-2 function is crucial, considering a vaccination targeting cells with stemness properties would be highly effective in contrast to a therapy targeting differentiated melanoma cells. Analysing over 200 melanomas including primaries, partly matched metastases and patients' cell cultures we show that TRP-2 is correlated with Melan A expression and decreases with tumor progression. In mice it is expressed in differentiated melanocytes as well as in stem cells. Furthermore, we identify a TRP-2 negative, proliferative, hypoxia related cell subpopulation which is significantly associated with tumor thickness and diseases progression. Patients with a higher percentage of those cells have a less favourable tumor specific survival. Our findings underline that TRP-2 is a differentiation antigen, highlighting the importance to combine TRP-2 vaccination with other strategies targeting the aggressive undifferentiated hypoxia related subpopulation.

• 出版日期2014-4