Title

 

Authors

L. Bizzozero¹, D. Cazzato¹, E. Assi¹, D. Cervia², C. Verdelli¹, E. Clementi^1,3, C. Perrotta<sup>1

1</sup>Department of Clinical Sciences, H. L. Sacco-University of Milan, Milano, Italy;²Department of Environmental Sciences, University of Tuscia, Viterbo, Italy;  ³E. Medea Scientific Institute,Bosisio Parini, Italy

 

Abstract

Defective apoptosis represents one of the major causative factors in the development and progression of cancer. The ability of tumor cells to evade engagement of apoptosis can play a significant role in their resistance to conventional therapeutic regimens. In the last few years, preclinical and clinical studies have indicated ceramide and the enzymes of its metabolism, in particular Acid Sphingomyelinase (A-SMase), as key players in tumor physiopathology. A-SMase is responsible for the hydrolysis of sphingomyelin to ceramide and phosphocoline and contributes significantly to the activation of  the apoptotic pathway, induced by different chemotherapeutic drugs as cisplatin, retinoids and doxorubicin, and UV radiation increasing their efficacy.
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. In order to investigate a possible correlation between A-SMase expression and B16 cells phenotype we isolated several B16 clones on the basis of 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 experiments showed that the white and the black clones differ in terms of growth rate, invasiveness and histological characteristics. These data suggest that A-SMase is fundamental for melanoma cells phenotype and behavior determination and it might be considered a potential “marker” of tumor malignant progression and a protein to be further investigated in perspective of new and more effective anticancer strategies.