Nikitovic Dragana, Kouvidi Katerina, Kavasi Rafaela-Maria, Berdiaki Aikaterini, Tzanakakis George N
Department of Anatomy- Histology-Embryology, Faculty of Medicine, University of Crete, P.O. Box: 71003, Heraklion, Greece.
Curr Drug Deliv. 2016;13(4):500-11. doi: 10.2174/1567201813666151109103013.
Hyaluronan (HA), a glycosaminoglycan, is a key extracellular matrix (ECM) component, and has been established to contribute to fibrotic, angiogenic, inflammatory as well as processes supporting cancer development. The changes in HA deposition in different tumors have been widely studied. Indeed, a multitude of reports demonstrate that HA expression is increased in different neoplasmatic tissues including lung, colon, prostate and breast cancer. The aims of this paper are to critically and in depth discuss aspects of HA metabolism in cancer and recent developments of its utilization in cancer therapy.
Up to date research and online content are reviewed.
The cellular roles of HA are perpetrated through molecular interactions with HA-binding proteins, called hyaladherins, including CD44 receptor as well as receptor for hyaluronan-mediated motility (RHAMM). HA binding can be followed by receptor-mediated endocytosis. Importantly, hyaladherins show an altered expression in tumor tissues. Indeed, post-translational alterations in CD44 structure have been suggested to regulate the equilibrium between the "inactive" low affinity state and the "active" high affinity state of the HA binding capacity. In this concept HA fragments can be utilized as specific targeting ligands for efficient and safe drug delivery in cancer.
HA-drug bioconjugates and nanoparticles have emerged as a promising platform for drug delivery during cancer treatment as demonstrated in various pre-clinical studies. Recent developments from clinical trials indicate that the utilization of specific HA-drug bioconjugates might be approved for the medical practice in the nearest future.
透明质酸（HA）是一种糖胺聚糖，是细胞外基质（ECM）的关键成分，已被证实有助于纤维化、血管生成、炎症以及支持癌症发展的过程。不同肿瘤中HA沉积的变化已得到广泛研究。事实上，大量报告表明，HA在包括肺癌、结肠癌、前列腺癌和乳腺癌在内的不同肿瘤组织中表达增加。本文旨在批判性地深入讨论癌症中HA代谢的各个方面及其在癌症治疗中的最新应用进展。
综述了最新的研究和在线内容。
HA的细胞作用是通过与HA结合蛋白（称为透明质酸黏附素）的分子相互作用来实现的，包括CD44受体以及透明质酸介导的运动受体（RHAMM）。HA结合后可通过受体介导的内吞作用进行。重要的是，透明质酸黏附素在肿瘤组织中的表达发生改变。事实上，有人提出CD44结构的翻译后改变可调节HA结合能力的“非活性”低亲和力状态和“活性”高亲和力状态之间的平衡。在这一概念中，HA片段可作为特异性靶向配体，用于癌症中高效、安全的药物递送。
正如各种临床前研究所表明的，HA-药物生物共轭物和纳米颗粒已成为癌症治疗中一种有前景的药物递送平台。临床试验的最新进展表明，特定的HA-药物生物共轭物的应用可能在不久的将来被批准用于医疗实践。
