Oral communication, CS10 / C44

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Uncovered role of Tyrosinase-related Protein 1 (TYRP1) in melanoma cells aggressiveness

TYRP1 is the most abundant glycoprotein in melanocytic cells and has been involved in pigmentation. While the murine protein has been reported as a DHICA-oxidase enzyme in the eumelanin pathway, the exact role of human TYRP1 remains unclear. We quantified TYRP1 transcript levels by RT-qPCR in a cohort of 62 metastatic melanoma biopsies, what led us to distinguish two subgroups according to high and low expression levels of TYRP1. These results were consistent with recent data obtained by G. Ghanem’s group from J Bordet Institute (Belgium): they demonstrated that metastatic melanomas with high levels of TYRP1 mRNA were correlated to overall survivals lower than 30 months. Thus, to address the question of a potential link between TYRP1 expression levels and melanoma outcome, we adopted an RNA-interference strategy using lentivirus encoding short hairpin RNA (shRNA) to knock-down TYRP1 expression in three melanoma cell lines derived from vertical-growth phase (VGP) and metastatic tumors. TYRP1 depletion resulted in dramatic morphological changes and cytoskeleton remodeling. Moreover, shTYRP1 cells displayed decreased proliferation, migration and invasion abilities, but no cell death. Such consequences were not observed when TYRP1-negative melanoma cells were infected with shTYRP1-lentivirus, indicating that this phenotype is specific to TYRP1 knock-down. Altogether, these results show that TYRP1 modulates the aggressiveness of melanoma cells and raise the question of another function for this protein, what is currently under deep investigation.

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