Diverse expression of N-acetylglucosaminyltransferase V and complex-type β1,6-branched N-glycans in uveal and cutaneous melanoma cells

Abstract

Although both uveal (UM) and cutaneous (CM) melanoma cells derive from the transformed melanocytes, their biology varies significantly in several aspects. Malignant transformation is frequently associated with alternations in cell glycosylation, in particular those concerning branched complex-type N-glycans. These changes occur principally in β1,4-N-acetylglucosaminyltransferase III (GnT-III) that catalyzes the synthesis of glycans with bisected N-acetylglucosamine (GlcNAc) and β1,6-N-acetylglucosaminyltransferase V (GnT-V) that is involved in forming β1,6-branched antenna in complex-type glycans. We searched for the reasons of a different behavior of CM and UM cells in the expression of GnT-III and GnT-V and their oligosaccharide products. Our study showed that UM cells have more β1,6-branched glycans than CM cells, what results from a higher expression of MGAT5 gene encoding GnT-V. The higher β1,6-branching of glycans in UM may contribute to their higher potential to migrate on fibronectin and weaker binding to main extracellular matrix proteins, observed in our previous studies.

An Insight into the Proteome of Uveal Melanoma-Derived Ectosomes Reveals the Presence of Potentially Useful Biomarkers

“…Glycans play a fundamental role during tumor cell dissociation and invasion, mainly by interfering with intercellular signaling and cell–cell adhesion. For instance, higher expression of β1,6-branched N-glycans interferes with UM cells migration and causes their weaker binding to fibronectin and vitronectin [34,35,36]. In the present study, β1,6-branched and complex type N-glycans with bisecting GlcNAc were detected in Mel202-derived ectosomes and several PHA-L- and PHA-E-positive bands showed a significant enrichment.…”

The Role of Glycosylation in Melanoma Progression

“…Cell surface N-glycans with GlcNAc β1,6 branches have also been shown to contribute to uveal melanoma progression by enhancing cell motility [80]. This could be in part explained by a more abundant presence of GlcNAc β1,6-branched N-glycans and higher expression of MGAT5 in uveal compared to cutaneous melanoma cell lines, contributing to their ability to migrate in fibronectin [81].…”

Melanoma‐associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target*

“…In melanoma, altered glycosylation has been documented to have a profound effect on metastatic processes 24–27 . For example, metastatic melanomas feature elevated levels of mannosyl‐β1,6 N ‐acetylglucosaminyltransferase 5 (MGAT5) and corresponding β1‐6 N ‐glycan branching product on the adhesion receptor α V β 3 integrin, which enhances tumour angiogenesis and metastasis 24,25 .…”

“…19,22,23 In melanoma, altered glycosylation has been documented to have a profound effect on metastatic processes. [24][25][26][27] For example, metastatic melanomas feature elevated levels of mannosyl-b1,6 N-acetylglucosaminyltransferase 5 (MGAT5) and corresponding b1-6 N-glycan branching product on the adhesion receptor a V b 3 integrin, which enhances tumour angiogenesis and metastasis. 24,25 Moreover, in murine melanoma cell lines, highly metastatic subclones express increased cell-surface a2-6 sialylation, while poorly metastasizing subclones display increased a1-3 fucosylation.…”

“…[24][25][26][27] For example, metastatic melanomas feature elevated levels of mannosyl-b1,6 N-acetylglucosaminyltransferase 5 (MGAT5) and corresponding b1-6 N-glycan branching product on the adhesion receptor a V b 3 integrin, which enhances tumour angiogenesis and metastasis. 24,25 Moreover, in murine melanoma cell lines, highly metastatic subclones express increased cell-surface a2-6 sialylation, while poorly metastasizing subclones display increased a1-3 fucosylation. 26,27 Additionally, analysis of patient samples of melanoma implicates a1,6 fucosyltransferase FUT8 as a driver of metastasis.…”