Targeting Glycans and Heavily Glycosylated Proteins for Tumor Imaging.
Targeting Glycans and Heavily Glycosylated Proteins for Tumor Imaging.
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DOI：
10.3390/cancers12123870
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发表时间：
2020-12-21
期刊：
影响因子：
5.2
通讯作者：
Sier CFM
中科院分区：
文献类型：
--
作者：
Houvast RD;Vankemmelbeke M;Durrant LG;Wuhrer M;Baart VM;Kuppen PJK;de Geus-Oei LF;Vahrmeijer AL;Sier CFM
区分恶性肿瘤和健康组织是肿瘤外科手术的关键。手术中有针对性的成像有助于外科医生更好地操作。目前用于检测癌症的示踪剂是针对肿瘤细胞膜上过表达的蛋白质。这篇综述评估了肿瘤相关糖分子作为蛋白质成像癌组织的替代品的使用。这些糖分子以聚糖形式存在于糖基化膜蛋白和糖脂上。由于它们的位置和每个细胞中大量的糖分子，这些糖分子可能是比蛋白质更好的肿瘤成像目标。实时肿瘤成像技术越来越多地应用于肿瘤手术，但仍需要补充新的靶向示踪剂，提供基于肿瘤内过程或蛋白质表达的特异性肿瘤组织检测。为了最大限度地提高肿瘤/非肿瘤的对比，靶点应该只在肿瘤组织中高度均匀地表达，最好是从最早的发育阶段开始。不幸的是，大多数评估的肿瘤相关蛋白似乎不符合所有这些标准。因此，对理想目标的追求仍在继续。蛋白质和脂质的异常糖基化是几乎所有癌症类型的基本标志，并有助于肿瘤进展。此外，还观察到携带异常聚糖（如粘蛋白和蛋白聚糖）的糖蛋白过表达。选定的肿瘤相关糖抗原大量表达，因此可以成为靶向肿瘤成像的理想候选者。然而，基于聚糖的肿瘤成像仍处于起步阶段。在这篇综述中，我们通过讨论该领域的临床前和临床成就，强调了聚糖、重度糖基化蛋白聚糖和粘蛋白作为多模式肿瘤成像靶点的潜力。此外，我们描述了靶向聚糖与癌症相关蛋白相比的主要优点和局限性。最后，通过简要概述与各自肿瘤类型相关的最具吸引力的肿瘤相关聚糖和糖基化蛋白，我们提出了在临床实践中实施基于聚糖的成像的方法。
Distinguishing malignancy from healthy tissue is essential for oncologic surgery. Targeted imaging during an operation aids the surgeon to operate better. The present tracers for detecting cancer are directed against proteins that are overexpressed on the membrane of tumor cells. This review evaluates the use of tumor-associated sugar molecules as an alternative for proteins to image cancer tissue. These sugar molecules are present as glycans on glycosylated membrane proteins and glycolipids. Due to their location and large numbers per cell, these sugar molecules might be better targets for tumor imaging than proteins. Real-time tumor imaging techniques are increasingly used in oncological surgery, but still need to be supplemented with novel targeted tracers, providing specific tumor tissue detection based on intra-tumoral processes or protein expression. To maximize tumor/non-tumor contrast, targets should be highly and homogenously expressed on tumor tissue only, preferably from the earliest developmental stage onward. Unfortunately, most evaluated tumor-associated proteins appear not to meet all of these criteria. Thus, the quest for ideal targets continues. Aberrant glycosylation of proteins and lipids is a fundamental hallmark of almost all cancer types and contributes to tumor progression. Additionally, overexpression of glycoproteins that carry aberrant glycans, such as mucins and proteoglycans, is observed. Selected tumor-associated glyco-antigens are abundantly expressed and could, thus, be ideal candidates for targeted tumor imaging. Nevertheless, glycan-based tumor imaging is still in its infancy. In this review, we highlight the potential of glycans, and heavily glycosylated proteoglycans and mucins as targets for multimodal tumor imaging by discussing the preclinical and clinical accomplishments within this field. Additionally, we describe the major advantages and limitations of targeting glycans compared to cancer-associated proteins. Lastly, by providing a brief overview of the most attractive tumor-associated glycans and glycosylated proteins in association with their respective tumor types, we set out the way for implementing glycan-based imaging in a clinical practice.
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