Hyaluronan regulation of endothelial barrier function in cancer.
Hyaluronan regulation of endothelial barrier function in cancer.
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DOI：
10.1016/b978-0-12-800092-2.00007-1
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发表时间：
2014
影响因子：
--
通讯作者：
Singleton, Patrick A.
中科院分区：
文献类型：
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作者：
Singleton, Patrick A.
血管完整性或维持血管连续性是由内皮细胞-细胞连接调节的基本过程。内皮屏障功能缺陷是包括肿瘤、血管生成和转移在内的多种疾病过程的始动因素。糖胺聚糖，透明质酸(HA)，通过特定的机制来维持血管的完整性，包括HA结合蛋白在富含小窝的微域中的信号传递，小窝是脂筏的一个子集。某些疾病状态，包括癌症，会增加酶促透明质酸酶活性和产生活性氧物种，从而将高分子量透明质酸(HMW-HA)分解为低分子量片段(LMW-HA)。LMW-HA可以在肿瘤进展过程中激活特定的HA结合蛋白，促进内皮细胞与细胞之间的接触中断。相反，外源性给予HMW-HA可促进血管完整性的增强。根据HA的大小和存在的HA结合蛋白，本文综述了HA在调节血管生成和转移过程中的作用。此外，还讨论了HMW-HA在癌症治疗中的潜在治疗应用。
Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated by endothelial cell–cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including tumor angiogenesis and metastasis. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through specific mechanisms including HA-binding protein signaling in caveolin-enriched microdomains, a subset of lipid rafts. Certain disease states, including cancer, increase enzymatic hyaluronidase activity and reactive oxygen species generation, which break down high molecular weight HA (HMW-HA) to low molecular weight fragments (LMW-HA). LMW-HA can activate specific HA-binding proteins during tumor progression to promote disruption of endothelial cell–cell contacts. In contrast, exogenous administration of HMW-HA promotes enhancement of vascular integrity. This review focuses on the roles of HA in regulating angiogenic and metastatic processes based on its size and the HA-binding proteins present. Further, potential therapeutic applications of HMW-HA in treating cancer are discussed.