Biophysical characterization of melanoma cell phenotype markers during metastatic progression

Abstract

Melanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods.

Keywords: Glycosylation; Label-free techniques; Melanoma; Metabolism; Metastasis.

Fig. 1

The connection between various pathways in cells: glycolysis, OXPHOS, TME signaling, HBP and glycan biosynthesis pathway

Fig. 2

Biophysical characterization of glycans present on melanocytes/melanoma cells by means of label-free methods: AFM after tip functionalization with lectin (a) and QCM-D during the measurement with lectin (b). Schematic representation of the distinction of melanoma cells with a higher metastatic potential from the cells with a lower metastatic potential based on the performed measurements of lectin binding to glycans on cells by means of AFM/QCM-D (c)