THE ROLE OF ACID SPHINGOMYELINASE IN MELANOMA DEVELOPMENT AND PROGRESSION

Recent studies show that sphingolipids and the enzymes responsable for their intracellular metabolism are important in cellular processes such as proliferation, apoptosis and differentiation. Recent evidence suggested a role for this enzymes in tumorigenesis. In particular, Acid sphingomyelinase (A-SMase) plays pivotal role in tumor biology and tumor response to chemotherapeutic drugs. We investigate the specific role of A-SMase expressed by melanoma B16 cells which show different tumorigenic and metastatic properties dependent on their melanin content. We isolated several B16 clones on the basis of their pigmentation, indicating the pigmented clones as “black”, and the not-pigmented as “white” and we observed a higher expression and activity of A-SMase in the white B16 clones. in vivo and in vitro experiments showed that the white and the black clones differ in terms of growth rate, metastatic capacity and histological characteristics. These data suggest a strong relationship between A-SMase expression and tumour behaviour. These studies suggest A-SMase as possible prognostic factor in tumor and might help refine therapeutic strategies against tumour based on regulation of A-SMase activity/expression.