Simpson Melanie A, Lokeshwar Vinata B
Department of Biochemistry, University of Nebraska, Lincoln, Nebraska, USA.
Front Biosci. 2008 May 1;13:5664-80. doi: 10.2741/3108.
Genitourinary cancers are the most frequently diagnosed cancers in men and the fifth most common in women. Management of disease through accurate and cost effective early diagnostic markers, as well as identification of valid prognostic indicators, has contributed significantly to improved treatment outcomes. In this review, we will discuss the function, regulation and clinical utility of hyaluronan (HA), genes encoding its metabolic enzymes and receptors that mediate its cellular effects. Specific HA synthase (HAS) and hyaluronidase (HAase) genes encode the enzymes that produce HA polymers and oligosaccharides, respectively. Differential effects of these enzymes in progression of genitourinary tumors are determined by the relative balance between HAS and HAase levels, as well as the distribution of receptors. The genes are regulated in a complex fashion at the transcriptional and post-translational levels, but also by epigenetic events, alternative mRNA splicing, and subcellular localization. Importantly, the major tumor-derived HAase enzyme, HYAL-1, either alone or together with HA, is an accurate diagnostic and prognostic marker for genitourinary tumors.
泌尿生殖系统癌症是男性中最常被诊断出的癌症，在女性中则是第五大常见癌症。通过准确且具有成本效益的早期诊断标志物来管理疾病，以及识别有效的预后指标，对改善治疗结果做出了重大贡献。在本综述中，我们将讨论透明质酸（HA）、编码其代谢酶的基因以及介导其细胞效应的受体的功能、调节和临床应用。特定的透明质酸合酶（HAS）和透明质酸酶（HAase）基因分别编码产生HA聚合物和寡糖的酶。这些酶在泌尿生殖系统肿瘤进展中的不同作用取决于HAS和HAase水平之间的相对平衡以及受体的分布。这些基因在转录和翻译后水平以复杂的方式受到调节，同时也受到表观遗传事件、选择性mRNA剪接和亚细胞定位的影响。重要的是，主要的肿瘤源性HAase酶HYAL-1，无论是单独还是与HA一起，都是泌尿生殖系统肿瘤的准确诊断和预后标志物。
