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Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.bbagen.2020.129513
Martina Pirro 1 , Yoann Rombouts 2 , Alexandre Stella 2 , Olivier Neyrolles 2 , Odile Burlet-Schiltz 2 , Sandra J van Vliet 3 , Arnoud H de Ru 1 , Yassene Mohammed 1 , Manfred Wuhrer 1 , Peter A van Veelen 1 , Paul J Hensbergen 1
Affiliation  

BACKGROUND The Ca2+-dependent C-type lectin receptor Macrophage Galactose-type Lectin (MGL) is highly expressed by tolerogenic dendritic cells (DC) and macrophages. MGL exhibits a high binding specificity for terminal alpha- and beta-linked GalNAc residues found in Tn, sTn and LacdiNAc antigens. These glycan epitopes are often overexpressed in colorectal cancer (CRC), and, as such, MGL can be used to discriminate tumor from the corresponding healthy tissues. Moreover, the high expression of MGL ligands is associated with poor disease-free survival in stage III of CRC tumors. Nonetheless, the glycoproteins expressed by tumor cells that are recognized by MGL have hitherto remained elusive. METHODS Using a panel of three CRC cell lines (HCT116, HT29 and LS174T), recapitulating CRC diversity, we performed FACS staining and pull-down assays using a recombinant soluble form of MGL (and a mutant MGL as control) combined with mass spectrometry-based (glyco)proteomics. RESULTS HCT116 and HT29, but not LS174T, are high MGL-binding CRC cell lines. On these cells, the major cell surface binding proteins are receptors (e.g. MET, PTK7, SORL1, PTPRF) and integrins (ITGB1, ITGA3). From these proteins, several N- and/or O-glycopeptides were identified, of which some carried either a LacdiNAc or Tn epitope. CONCLUSIONS We have identified cell surface MGL-ligands on CRC cell lines. GENERAL SIGNIFICANCE Advances in (glyco)proteomics have led to identification of candidate key mediators of immune-evasion and tumor growth in CRC.

中文翻译:

结直肠癌细胞系中巨噬细胞半乳糖型凝集素(MGL)配体的表征。

背景技术Ca 2+依赖性C型凝集素受体巨噬细胞半乳糖型凝集素(MGL)由致耐受性树突状细胞(DC)和巨噬细胞高表达。MGL对在Tn,sTn和LacdiNAc抗原中发现的末端α和β连接的GalNAc残基表现出高结合特异性。这些聚糖表位通常在结直肠癌(CRC)中过表达,因此,MGL可用于区分肿瘤与相应的健康组织。此外,MGL配体的高表达与CRC肿瘤的III期无病生存期差有关。尽管如此,迄今为止,由MGL识别的肿瘤细胞表达的糖蛋白仍然难以捉摸。方法使用一组三个CRC细胞系(HCT116,HT29和LS174T)概括CRC多样性,我们使用重组可溶性形式的MGL(和突变MGL作为对照)结合基于质谱的(糖类)蛋白质组学进行了FACS染色和下拉分析。结果HCT116和HT29是高MGL结合CRC细胞系,但不是LS174T。在这些细胞上,主要的细胞表面结合蛋白是受体(例如MET,PTK7,SORL1,PTPRF)和整联蛋白(ITGB1,ITGA3)。从这些蛋白质中,鉴定出几种N-和/或O-糖肽,其中一些带有LacdiNAc或Tn表位。结论我们已经确定了CRC细胞系上的细胞表面MGL-配体。一般意义(糖)蛋白质组学的进展已导致识别CRC中免疫逃逸和肿瘤生长的候选关键介体。结果HCT116和HT29是高MGL结合CRC细胞系,但不是LS174T。在这些细胞上,主要的细胞表面结合蛋白是受体(例如MET,PTK7,SORL1,PTPRF)和整联蛋白(ITGB1,ITGA3)。从这些蛋白质中,鉴定出几种N-和/或O-糖肽,其中一些带有LacdiNAc或Tn表位。结论我们已经确定了CRC细胞系上的细胞表面MGL-配体。一般意义(糖)蛋白质组学的进展已导致识别CRC中免疫逃逸和肿瘤生长的候选关键介体。结果HCT116和HT29是高MGL结合CRC细胞系,但不是LS174T。在这些细胞上,主要的细胞表面结合蛋白是受体(例如MET,PTK7,SORL1,PTPRF)和整联蛋白(ITGB1,ITGA3)。从这些蛋白质中,鉴定出几种N-和/或O-糖肽,其中一些带有LacdiNAc或Tn表位。结论我们已经确定了CRC细胞系上的细胞表面MGL-配体。一般意义(糖)蛋白质组学的进展已导致识别CRC中免疫逃逸和肿瘤生长的候选关键介体。其中一些携带LacdiNAc或Tn表位。结论我们已经确定了CRC细胞系上的细胞表面MGL-配体。一般意义(糖)蛋白质组学的进展已导致识别CRC中免疫逃避和肿瘤生长的候选关键介体。其中一些携带LacdiNAc或Tn表位。结论我们已经确定了CRC细胞系上的细胞表面MGL-配体。一般意义(糖)蛋白质组学的进展已导致识别CRC中免疫逃避和肿瘤生长的候选关键介体。
更新日期:2020-01-04
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