Abstract
We investigated the correlation between metastatic behaviors of tumor cells and asparagine‐linked glycosylation (N‐glycosylation) of tumor‐derived extracellular vesicles (EVs). Three mouse melanoma B16 variants with distinct metastatic potentials show similar gene expression levels and enzymatic activities of glycosyltransferases involved in N‐glycosylation. All melanoma variants and EVs have nearly identical profiles of de‐sialylated N‐glycans. The major de‐sialylated N‐glycan structures of cells and EVs are core‐fucosylated, tetra‐antennary N‐glycans with β1,6‐N‐acetylglucosamine branches. A few N‐glycans are extended by N‐acetyllactosamine repeats. Sialylation of these N‐glycans may generate cell‐type‐specific N‐glycomes on EVs. Taken together, melanoma‐derived EVs show high expression of tumor‐associated N‐glycans, and the core structure profile is inherited during multiple selection cycles of B16 melanomas and from tumor cells to EVs.
Highlights
Yoichiro Harada1, Yasuhiko Kizuka2, Yuko Tokoro2, Kiyotaka Kondo3, Hirokazu Yagi4, Koichi Kato4,5, Hiromasa Inoue3, Naoyuki Taniguchi6 and Ikuro Maruyama1
Three mouse melanoma B16 variants with distinct metastatic potentials show similar gene expression levels and enzymatic activities of glycosyltransferases involved in N-glycosylation
To clarify the gene expression landscapes in three B16 variants with distinct metastatic potentials (B16-F1, B16-F10, B16-BL6), the expression levels of 144 glycosyltransferase genes were analyzed by real-time PCR (Fig. S1 and Table S1) and those involved in N-glycosylation were shown in Fig. 1A and Table 1
Summary
A few N-glycans are extended by N-acetyllactosamine repeats Sialylation of these N-glycans may generate cell-type-specific N-glycomes on EVs. Taken together, melanoma-derived EVs show high expression of tumor-associated N-glycans, and the core structure profile is inherited during multiple selection cycles of B16 melanomas and from tumor cells to EVs. Most cell surface and secretory proteins are modified by asparagine-linked glycans (N-glycans) [1], which play indispensable roles in regulation of protein quality control, intracellular trafficking, and cell-to-cell communication. Blood-borne tumor metastasis is a complex process involving tumor cell invasion into normal tissues, intravasation to the circulation, extravasation, and colonization at distant organs [11] To investigate these processes, multiple in vivo and in vitro selections have been performed to obtain mouse B16 malignant melanoma variants with distinct metastatic potentials. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
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