Berdiaki Aikaterini, Neagu Monica, Giatagana Eirini-Maria, Kuskov Andrey, Tsatsakis Aristidis M, Tzanakakis George N, Nikitovic Dragana
Laboratory of Histology-Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece.
Department of Immunology, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania.
Biomolecules. 2021 Mar 8;11(3):395. doi: 10.3390/biom11030395.
The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics. This review will comprehensively discuss recent developments and the broad potential of GAG utilization for cancer therapy.
肿瘤微环境（TME）由癌细胞、非癌细胞、基质细胞和免疫细胞组成，这些细胞被细胞外基质（ECM）成分所包围。糖胺聚糖（GAGs）是天然生物大分子，是重要的ECM和细胞膜成分，在癌组织中广泛改变。在疾病进展过程中，GAG的精细结构以与疾病演变相关的方式发生变化。因此，GAG硫酸化模式的变化与恶性转化直接相关。它们的分子量、分布、组成和精细修饰（包括硫酸化）在癌症发展过程中表现出明显改变。由于GAGs和基于GAG的分子具有独特性质，它们被认为是抗癌治疗的有前景的效应物。考虑到它们参与肿瘤发生，其在药物开发中的应用一直是工业界和学术研究努力的重点。这些努力主要朝着两个方向发展：（i）将GAGs用作治疗策略的靶点；（ii）利用GAGs的特异性和优异的物理化学性质进行癌症治疗药物的靶向递送。本综述将全面讨论GAGs在癌症治疗中的最新进展和广泛潜力。
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