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黏蛋白 1 经唾液酸化核心 2 O-聚糖修饰后的表达和定位在黏液表皮样癌中的研究。

Expression and localisation of MUC1 modified with sialylated core-2 O-glycans in mucoepidermoid carcinoma.

机构信息

Department of Oral Oncology, Oral and Maxillofacial Surgery, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa-Shi, Chiba, 272-8513, Japan.

Department of Pathology and Laboratory Medicine, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa-Shi, Chiba, 272-8513, Japan.

出版信息

Sci Rep. 2023 Apr 8;13(1):5752. doi: 10.1038/s41598-023-32597-2.

Abstract

Mucoepidermoid carcinoma (MEC) is the most frequent of the rare salivary gland malignancies. We previously reported high expression of Mucin 1 (MUC1) modified with sialylated core-2 O-glycans in MEC by using tissue homogenates. In this study, we characterised glycan structures of MEC and identified the localisation of cells expressing these distinctive glycans on MUC1. Mucins were extracted from the frozen tissues of three patients with MEC, and normal salivary glands (NSGs) extracted from seven patients, separated by supported molecular matrix electrophoresis (SMME) and the membranes stained with various lectins. In addition, formalin-fixed, paraffin-embedded sections from three patients with MEC were subjected to immunohistochemistry (IHC) with various monoclonal antibodies and analysed for C2GnT-1 expression by in situ hybridisation (ISH). Lectin blotting of the SMME membranes revealed that glycans on MUC1 from MEC samples contained α2,3-linked sialic acid. In IHC, MUC1 was diffusely detected at MEC-affected regions but was specifically detected at apical membranes in NSGs. ISH showed that C2GnT-1 was expressed at the MUC1-positive in MEC-affected regions but not in the NSG. MEC cells produced MUC1 modified with α2,3-linked sialic acid-containing core-2 O-glycans. MUC1 containing these glycans deserves further study as a new potential diagnostic marker of MEC.

摘要

黏液表皮样癌(MEC)是最常见的罕见涎腺癌。我们之前曾报道过在 MEC 中,通过使用组织匀浆,MUC1 上的唾液酸化核心 2 O-聚糖修饰物的高表达。在这项研究中,我们对 MEC 的聚糖结构进行了表征,并确定了表达这些独特聚糖的 MUC1 细胞的定位。从三名 MEC 患者的冷冻组织和七名正常涎腺(NSG)患者的组织中提取黏蛋白,通过支持分子基质电泳(SMME)分离,并使用各种凝集素对膜进行染色。此外,对三名 MEC 患者的福尔马林固定、石蜡包埋切片进行各种单克隆抗体的免疫组织化学(IHC)分析,并通过原位杂交(ISH)分析 C2GnT-1 的表达。SMME 膜上的凝集素印迹显示 MEC 样本中 MUC1 上的聚糖含有α2,3 连接的唾液酸。在 IHC 中,MUC1 在 MEC 受累区域呈弥漫性表达,但在 NSG 中呈顶膜特异性表达。ISH 显示 C2GnT-1 在 MEC 受累区域的 MUC1 阳性区域表达,但在 NSG 中不表达。MEC 细胞产生了含有α2,3 连接唾液酸化核心 2 O-聚糖的 MUC1。含有这些聚糖的 MUC1 值得进一步研究,作为 MEC 的一种新的潜在诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e196/10082819/35fea8b6e3ff/41598_2023_32597_Fig1_HTML.jpg

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