An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative |
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Authors: | Daniela Lenggenhager Alessandra Curioni-Fontecedro Martina Storz Olga Shakhova Lukas Sommer Daniel S Widmer Burkhardt Seifert Holger Moch Reinhard Dummer Daniela Mihic-Probst |
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Institution: | 2. Department of Oncology, University Hospital, Zurich, Switzerland;3. Institute of Anatomy, University of Zurich, Zurich, Switzerland;4. Clinic of Dermatology, University Hospital, Zurich, Switzerland;5. Division of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland |
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Abstract: | 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. |
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