Recent studies show that sphingolipids and the enzymes responsable for their intracellular metabolism are important in cellular processes such as proliferation, apoptosis and differentiation, thus suggesting their role in tumorigenesis. In particular, acid sphingomyelinase (A-SMase) plays pivotal role in tumor biology and tumor response to chemotherapeutic drugs. We investigated the specific role of A-SMase expressed by mouse melanoma B16 cells which show different tumorigenic and metastatic properties dependent on their melanin content.

Several B16 clones were isolated, indicating the pigmented clones as "black", and the not-pigmented as "white". The white clones showed a higher A-SMase expression/activity respect to black clones. Both in vitro and in vivo experiments indicated that the white and the black clones differ in terms of growth rate, viability/proliferation, histological characteristics, tumour progression/invasion and metastatic capacity. In particular, black clones appear to have more tumorigenic properties than white clones, thus indicating a negative correlation between A-SMase activity and cancer progression.

Our data suggest a strong relationship between A-SMase and biology of tumours, indicating this enzyme as possible prognostic factor in melanomas, and might help refine therapeutic strategies against cancer based on regulation of A-SMase activity/expression.