Anandamide-Modulated Changes in Metabolism, Glycosylation Profile and Migration of Metastatic Melanoma Cells

SIMPLE SUMMARY: Anandamide (AEA) belongs to the group of endocannabinoids and possesses various regulatory properties in physiological as well as pathological processes occurring in the organism. In this research some basic biological tests were applied to investigate AEA-induced changes in cell metabolism and motility, as well as advanced biophysical methods for the determination of the differences in the cell glycosylation profile on a highly dangerous model of melanoma skin cancer, for which an effective therapy is not yet available. Our research suggests that anandamide treatment of metastatic melanoma cells increases the cell metabolism which leads to the reduction in the metastatic potential of cells in terms of the cell glycosylation profile and cell migration. In the view of our research, it can be presumed that anandamide usage in the combined therapy of advanced melanoma would be an advantage for the patient. ABSTRACT: An effective therapy for advanced melanoma, a skin cancer with the highest mortality, has not yet been developed. The endocannabinoid system is considered to be an attractive target for cancer treatment. The use of endocannabinoids, such as anandamide (AEA), is considered to be much greater than as a palliative agent. Thus, we checked its influence on various signaling pathways in melanoma cells. Our investigation was performed on four commercial cell lines derived from different progression stages (radial WM35 and vertical WM115 growth phases, lymph node WM266-4 metastasis, solid tumor A375-P metastasis). Cell viability, glucose uptake, quantification of reactive oxygen species production, expression of selected genes encoding glycosyltransferases, quantification of glycoproteins production and changes in the glycosylation profile and migration, as well as in cell elastic properties were analyzed. The cell glycosylation profile was investigated using the biophysical profiling method—the quartz crystal microbalance with dissipation monitoring (QCM-D). Anandamide treatment of only metastatic cells resulted in: an increase in the cell metabolism, a decrease in GFAT-1 and DPM1 expression, followed by a decrease in L1-CAM glycoprotein production, which further influenced the reduction in the cell glycosylation profile and migration. Considering our results, AEA usage is highly recommended in the combined therapy of advanced melanoma.