Resumo

Over the past years, the physiological role of the cellular prion protein (PrPC) has been target of intensive studies, many of which point to a possible function of PrPC in cell-matrix adhesion and tumor progression. Matrix Metalloproteinases (MMPs) are secreted proteases capable of remodeling the extracellular matrix architecture, thereby modulating cell adhesion, migration and metastasis. Since both PrPC and MMPs are highly expressed in the central nervous system and are involved with similar cellular behavior, we hypothesized a possible cross-talking between them. In order to investigate our hypothesis, human embryonic kidney cells (HEK 293T) were transfected with expression vectors to produce GFP-PrPC and PrPC-3F4 and culture medium conditioned over 24 hours. Culture supernatant samples were analyzed for MMP-9 expression and activity by Western Blot and zymography. In PrPC-transfected cells MMP-9 expression and activity were decreased. Simultaneously, in GFP-PrPC and PrPC-3F4 transfected cells, we observed an increase in TIMP-1 expression, a classical MMP inhibitor. In conclusion, PrPC down-regulates MMP-9 and induces TIMP-1 expression in HEK 293T cells. The impact of MMP-9 activity modulation by prion protein in cell adhesion and tumor progression will be addressed in future experiments.