Gnagliosides and Sex Hormones in Human Melanoma

Abstract

Background. Malignant melanoma is the most aggressive form of skin cancer with a rapidly increasing incidence rate. In contrast to other tumors, the role of sex steroid hormones in the initiation and progression of melanoma remains unclear.Objective. To assess the interaction between the content and composition of gangliosides and sex steroid hormones 17βestradiol (E2) and testosterone (T) in malignant melanoma.Patients and methods. The analysis included 45 melanoma patients (age 28-86; 14 men, 15 non -pregnant women in mid follicular phase and 16 postmenopausal women) and 46 healthy controls. Serum levels of gangliosides (GM1-3, GD1 a,b ,2,3, GT1b, GQ1b), estradiol, testosterone measured in serum by chromatographic and immunochemiluminescence methods were correlated with sex and age.Results. Steroid hormones levels showed no differences between groups (p>0.05), while total gangliosides in normal serum were significantly lower than total ganglioside concentrations determined in melanoma samples (18.63 ± 3.17 mg/dL versus 74.82 ± 34.56 mg/dL) (p<0.05). There were no differences related to sex or age within groups regarding total gangliosides levels. Gangliosides pattern in melanoma patients compared to control showed lower GM3, higher GD3, lower GM3/GD3 ratio, increased GD2 levels, and no significant variation of GM1, GM2, GD1a, GT1b gangliosides. There is a positive correlation between estradiol levels and total gangliosides concentration both in non-pregnant premenopausal and postmenopausal melanoma patients. GM3 is negatively correlated with estradiol levels in melanoma group, GT1b and O-Acetyl GD3 concentrations are positively correlated with estradiol levels in women with melanoma. Testosterone levels showed no significant correlation with the content and pattern of gangliosides in melanoma patients.Conclusions. The correlations between content and composition of gangliosides and estradiol in melanoma suggest a possible role of these molecules in melanoma behavior.

Gangliosides and Antigangliosides in Malignant Melanoma

“…Based on this analysis, the authors found that low levels of circulating gangliosides are positive prognosis factors, in terms of increasing the relapse free survival in patients with malignant melanoma. These results justify the role of serum gangliosides as potential biomarkers in the management of patients with melanoma, a finding that supports previous researches [10,11,53,102,103].…”

“…New research directions developed in order to discover markers for early detection and therapeutic response of melanoma, treatments that could improve the survival rate. Recent studies showed that melanoma is a heterogeneous group of complex molecular disorders [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The diversity of these alterations sustain the importance of, on one hand, an individualized diagnosis, prognosis and treatment of melanoma patients, and, on the other hand, the detection of new biomarkers and therapeutic approaches in these patients.…”

“…Some of these genes are direct targets of HIF, while others are up-regulated by transcriptional factors HIF-dependent. Hypoxia interacts with transcriptional networks involved in lipid metabolism, including sterol response element binding proteins (SREBPs), DEC1/2 and GATA2/3 [9][10][11][48][49][50][51][52].…”

Heterogeneity of Gangliosides in Melanocytic Tumors

“…All data were evaluated using EpiInfo 2008. Details about the structure of the gangliosides used in this study were presented before (12).…”

Antiganglioside Antibodies and Inflammatory Response in Cutaneous Melanoma

“…Gangliosides are a group of bioactive glycolipids, located on the outer face of cell membranes. These glycolipids play a major role in cell proliferation, differentiation, migration, apoptosis, signal transduction, cell adhesion, modulating growth factor or hormone receptor, antigen recognition, protein trafficking, viral transformation, and oncogenesis [1][2][3][4][5]. Atypical expression of some ganglioside antigens associated with certain tumours (neuroblastomas, melanomas, gliomas, lymphomas, small cell lung cancer, and prostate cancer) and furthermore could play an important role in cancer immunotherapy [6][7][8].…”