Towards understanding the role of sialylation in melanoma progression

Abstract

Aberrant expression of sialic acids or altered linkage types is closely associated with malignant phenotype and metastatic potential, and can have prognostic significance in human cancer. The present study was undertaken to evaluate whether expression of sialylated derivatives on melanoma cell surface is associated with tumour progression. Four cell lines (WM1552C, WM115, IGR-39 and WM266-4) were used in the study. Cell surface expression of sialic acids was evaluated by flow cytometry with the use of Maackia amurensis and Sambucus nigra lectins. Moreover, adhesion and migration potential of melanoma cells and involvement of sialic acids in these processes were analysed. We have demonstrated that WM266-4 cells have a significantly higher level of α2,3-linked sialic acid residues than other cells, whereas IGR-39 cells had lower expression of α2,6-linked sialic acids. The adhesion efficiencies of WM1552C and WM115 cells were significantly lower than that of IGR-39 and WM266-4 cells. In contrast, WM266-4 cells repaired scratch wounds at least twice as fast as other cells. Melanoma cell adhesion to fibronectin in the presence of Sambucus nigra agglutinin (SNA) was reduced only in IGR-39 and WM266-4 cells, whereas the impact of Maackia amurensis agglutinin (MAA) on this process was much more important. Migration efficiency of melanoma cells was reduced more strongly in the presence of MAA than SNA. In conclusion, our results show that melanoma progression is associated with the increased expression of α2,3-linked sialic acids on the cell surface and these residues could promote melanoma cell interaction with fibronectin.

Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

“…Compared with substitutions at fucose C2 or C4 positions, modification at C3 enhanced uptake by tumor cells. As such, replacement of the OH group at C3 of fucose with OCH 2 COOH gave rise to better uptake and higher inhibitory effects on SW480 cells . Also, the carbamoyl group as substituent at various sites on the d ‐mannose moiety of BLM disaccharides showed that modification at C2 and C3 can afford a two‐ to fourfold increased efficiency in targeting in some cases, further implying that the hydroxy group at the C3 position of fucose and mannose is not required for tumor cell uptake.…”

“…l ‐Fucose‐anchored methotrexate‐loaded solid lipid nanoparticles (SLNs) have been designed to target breast cancer, and it was found that relative to free drug, in vivo maximum bioavailability and tumor targeting efficiency markedly increased, together with the minimum secondary drug distribution in various organs with the formulated and anchored nanocarrier . l ‐Fucose‐modified bovine serum albumin (BSA) was observed to preferentially target SW480 cells over hepatocyte or Kupffer cells in liver, and behaved as an excellent protein carrier . Cisplatin immobilized to dextran with the aid of a six‐membered chelate‐type coordination bond displayed significantly improved cytotoxic activity against colon 26 cancer cells in mice …”

Glycosylation in lymphoma: Biology and glycotherapy

“…Tunicamycin, a potent inhibitor of N‐glycosylation, appears to enhance HBL‐8 cell adhesion to fibronectin. Several studies have suggested that both glycosylation and sialic acid in integrins regulate integrin activity during tumor cell adhesion to extracellular matrix . Therefore, N‐glycans and sialic acid may be significant regulators for tumor cell adhesion to extracellular matrix, perhaps by altering the molecular conformation of integrin by steric hindrance, thereby modulating the function of integrin.…”

Increase of MAL-II Binding Alpha2,3-Sialylated Glycan Is Associated with 5-FU Resistance and Short Survival of Cholangiocarcinoma Patients

“…The increase of sialylation and sialylated-glycans were associated with development and progression of human diseases including cancer [10][11][12][13][14][15]. Sialylation plays important roles in tumor metastasis of many types of cancer such as colon [16], thyroid [14], and melanoma [17]. In addition, sialylation is involved in chemoresistance of ovarian [18,19], gastric [20], and colon [21] cancers.…”

“…Sialic binding lectins, such as Maackia amurensis lectin-II (MAL-II, α2,3-sialylated glycan binding lectin) and Sambucus nigra agglutinin (SNA, α2,6-sialylated glycan binding lectin), have been used for detecting and studying biological roles of sialylated-glycans in human diseases [9,11,12,14,15,17,[22][23][24][25].…”