Lokeshwar V B, Obek C, Soloway M S, Block N L
Department of Urology, University of Miami School of Medicine, Florida 33101, USA.
Cancer Res. 1997 Feb 15;57(4):773-7.
Hyaluronic acid (HA), a glycosaminoglycan, is known to promote tumor cell adhesion and migration, and its small fragments stimulate angiogenesis. We compared levels of HA in the urine of normal individuals and patients with bladder cancer or other genitourinary conditions, using a sensitive ELISA-like assay. Among the 144 specimens analyzed, the urinary HA levels of bladder cancer patients with G1 (255 +/- 41.7 ng/mg), G2 (291.8 +/- 68.3 ng/mg) and G3 (428.4 +/- 67 ng/mg) tumors are 4-9-fold elevated as compared to those of normal individuals (44.7 +/- 6.2 ng/mg) and patients with other genitourinary conditions (69.5 +/- 6.8 ng/mg; P < 0.001). Urinary HA measurement by the ELISA-like assay shows a sensitivity of 91.9% and specificity of 92.8% to detect bladder cancer. Thus, urinary HA measurement is a simple, noninvasive yet highly sensitive and specific method for bladder cancer detection. The increase in urinary HA concentration is a direct correlate of the elevated tumor-associated HA levels, because the HA levels are also elevated (3-5-fold) in bladder tumor tissues (P < 0.001). The profiles of urinary HA species of normal individuals and bladder cancer patients are different. Although only the intermediate-size HA species are found in the urine of normal and low-grade bladder tumor patients, the urine of high-grade bladder cancer patients contains both the high molecular mass and the small angiogenic HA fragments. These urinary HA fragments stimulate a mitogenic response (2.4-fold) in primary human microvessel endothelial cells, suggesting that the small HA fragments may regulate tumor angiogenesis by modulating endothelial cell functions.
透明质酸（HA）是一种糖胺聚糖，已知其可促进肿瘤细胞的黏附和迁移，其小片段可刺激血管生成。我们使用一种类似酶联免疫吸附测定（ELISA）的灵敏检测方法，比较了正常个体以及膀胱癌或其他泌尿生殖系统疾病患者尿液中的HA水平。在分析的144份样本中，G1期（255±41.7 ng/mg）、G2期（291.8±68.3 ng/mg）和G3期（428.4±67 ng/mg）膀胱癌患者尿液中的HA水平比正常个体（44.7±6.2 ng/mg）和其他泌尿生殖系统疾病患者（69.5±6.8 ng/mg；P<0.001）高出4至9倍。通过类似ELISA的检测方法测量尿液中的HA，检测膀胱癌的灵敏度为91.9%，特异性为92.8%。因此，尿液HA检测是一种简单、无创但高度灵敏且特异的膀胱癌检测方法。尿液中HA浓度的升高与肿瘤相关HA水平的升高直接相关，因为膀胱肿瘤组织中的HA水平也升高了（3至5倍）（P<0.001）。正常个体和膀胱癌患者尿液中HA种类的分布不同。虽然在正常和低级别膀胱肿瘤患者的尿液中仅发现中等大小的HA种类，但高级别膀胱癌患者的尿液中同时含有高分子量和小的促血管生成HA片段。这些尿液中的HA片段可刺激原代人微血管内皮细胞产生促有丝分裂反应（2.4倍），这表明小的HA片段可能通过调节内皮细胞功能来调控肿瘤血管生成。
