Department of Pharmacology, Medical University of Lodz, Żeligowskiego 7/9, PL 90-752 Łódź, Poland.
Pharmacol Rep. 2013;65(5):1056-74. doi: 10.1016/s1734-1140(13)71465-8.
The understanding of the role of hyaluronan in physiology and various pathological conditions has changed since the complex nature of its synthesis, degradation and interactions with diverse binding proteins was revealed. Initially perceived only as an inert component of connective tissue, it is now known to be involved in multiple signaling pathways, including those involved in cancer pathogenesis and progression. Hyaluronan presents a mixture of various length polymer molecules from finely fragmented oligosaccharides, polymers intermediate in size, to huge aggregates of high molecular weight hyaluronan. While large molecules promote tissue integrity and quiescence, the generation of breakdown products enhances signaling transduction, contributing to the pro-oncogenic behavior of cancer cells. Low molecular weight hyaluronan has well-established angiogenic properties, while the smallest hyaluronan oligomers may counteract tumor development. These equivocal properties make the role of hyaluronan in cancer biology very complex. This review surveys recent data on hyaluronan biosynthesis, metabolism, and interactions with its binding proteins called hyaladherins (CD44, RHAMM), providing themolecular background underlying its differentiated biological activity. In particular, the article critically presents current ideas on actual role of hyaluronan in cancer. The paper additionally maps a path towards promising novel anti-cancer therapeutics which target hyaluronan metabolic enzymes and hyaladherins, and constitute hyaluronan-based drug delivery systems.
自从揭示了透明质酸（hyaluronan，HA）的合成、降解及其与多种结合蛋白相互作用的复杂性质以来，人们对其在生理学和各种病理状况中的作用的理解发生了变化。最初仅被认为是结缔组织的一种惰性成分，现在已知它参与了多种信号通路，包括参与癌症发病机制和进展的信号通路。透明质酸呈现出各种长度聚合物分子的混合物，从精细片段化的寡糖到中等大小的聚合物，再到高分子量透明质酸的巨大聚集物。虽然大分子促进组织完整性和静止状态，但降解产物的产生增强了信号转导，有助于癌细胞的致癌行为。低分子量透明质酸具有明确的血管生成特性，而最小的透明质酸低聚物可能会对抗肿瘤的发展。这些模棱两可的特性使得透明质酸在癌症生物学中的作用非常复杂。本文综述了透明质酸生物合成、代谢及其与结合蛋白（称为透明质酸黏附素，CD44、RHAMM）相互作用的最新数据，为其分化的生物学活性提供了分子背景。特别是，本文批判性地介绍了透明质酸在癌症中的实际作用的当前观点。本文还为针对透明质酸代谢酶和透明质酸黏附素的有前途的新型抗癌治疗方法以及基于透明质酸的药物递送系统指明了方向。
