ABSTRACT
Title
Melanoma development and progression: the role of mitochondria
Authors
D. Cazzato1
1Department of Clinical Sciences L Sacco, Università di Milano, Milano, Italy;
DOTTORATO IN FARMACOLOGIA, CHEMIOTERAPIA E TOSSICOLOGIA MEDICHE
1Department of Clinical Sciences L Sacco, Università di Milano, Milano, Italy;
DOTTORATO IN FARMACOLOGIA, CHEMIOTERAPIA E TOSSICOLOGIA MEDICHE
Abstract
Malignant melanoma is a cancer composed by subpopulations of cells with various degrees of pigmentation. Pigmentation is an indicator for metabolic changes indeed, several studies show that highly pigmented melanoma tumours reside in aerobic microenviroments while hypo and amelanotic tumours have adapted to anaerobic conditions. A messenger involved in the regulation of melanogenesis and tumour expansion and response to chemotherapeutic drugs is the sphingolipid ceramide. recent studies investigating the effects of sphingolipid metabolites on melanogenesis, have demonstrated that C2-ceramide plays a role also in melanogenesis as it significantly decreases melanin content of cells through the down regulation of microphthalmia-associated transcription factor (MITF). In particular, the ceramide generating enzyme Acid sphingomyelinase (A-SMase), seems to be very important in melanogenesis besides of playing a pivotal role in tumor biology and in tumor response to stress.
Starting from this evidence, weisolated two melanoma B16 clones on the basis of their A-SMase expression and pigmentation and we investigated whether exists a correlation with mitochondrial metabolism and tumour growth. We focused our attention on the metabolic changes and mitochondrial morphology in melanoma B16 cells which show different tumorigenic and metastatic properties dependent on their melanin content and A-SMase expression. in vivo and in vitro experiments showed that the white and the black clones expressing higher or lower level of A-SMase respectively, differ in terms of growth rate and metastatic capacity. We also observed a higher oxygen consumption in the black B16 clones and, on the contrary, an increase in glycolitic ATP production in the white B16 clones. In addition, we found a strict connection between A-SMase expression and tumour growth and sensitivity to the chemotherapeutic drug, cisplatin. Taken together, these data suggest a relationship between metabolic characteristic and tumour behaviour and might help in prognosis and in therapeutic modalities of treatment.
Starting from this evidence, weisolated two melanoma B16 clones on the basis of their A-SMase expression and pigmentation and we investigated whether exists a correlation with mitochondrial metabolism and tumour growth. We focused our attention on the metabolic changes and mitochondrial morphology in melanoma B16 cells which show different tumorigenic and metastatic properties dependent on their melanin content and A-SMase expression. in vivo and in vitro experiments showed that the white and the black clones expressing higher or lower level of A-SMase respectively, differ in terms of growth rate and metastatic capacity. We also observed a higher oxygen consumption in the black B16 clones and, on the contrary, an increase in glycolitic ATP production in the white B16 clones. In addition, we found a strict connection between A-SMase expression and tumour growth and sensitivity to the chemotherapeutic drug, cisplatin. Taken together, these data suggest a relationship between metabolic characteristic and tumour behaviour and might help in prognosis and in therapeutic modalities of treatment.