Secretion of bladder tumor-derived hyaluronidase activity by invasive bladder tumor cells

Hyaluronic acid (HA), a glycosaminoglycan, promotes tumor metastasis and its small fragments are angiogenic. These small fragments are generated by degradation of HA by hyaluronidase (HAase). We measured urinary HAase levels of 196 individuals using an ELISA-like assay. The urinary HAase levels (31.1 +/- 3.7 mU/mg) of intermediate (G2) to high-grade (G3) bladder cancer patients are five- to seven-fold elevated as compared to those of normal individuals and patients with other genitourinary conditions or low-grade (G1) bladder cancer. The increase in urinary HAase levels is due to the secretion of a tumor-derived HAase which is elevated eight-fold in G2/G3 tumor tissues. The HAase in bladder tumor tissues is secreted by tumor epithelial cells and is associated with the invasive/metastatic potential of the tumor cells.