title: An Aggressive Hypoxia Related Subpopulation of Melanoma Cells is TRP-2 Negative.
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.
authors.affiliation: Institute of Surgical Pathology, University Hospital, Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lenggenhager
authors.affiliation: Department of Oncology, University Hospital, Zurich, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curioni-Fontecedro
authors.affiliation: Institute of Surgical Pathology, University Hospital, Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Storz
authors.affiliation: Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Shakhova
authors.affiliation: Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
authors.affiliation: Clinic of Dermatology, University Hospital, Zurich, Switzerland.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Widmer
authors.affiliation: Division of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Institute of Surgical Pathology, University Hospital, Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Clinic of Dermatology, University Hospital, Zurich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Institute of Surgical Pathology, University Hospital, Zurich, Switzerland. Electronic address: daniela.mihic@usz.ch.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic-Probst
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