EXPRESSION OF HYALURONIDASE BY TUMOR-CELLS INDUCES ANGIOGENESIS IN-VIVO

Hyaluronic acid is a proteoglycan present in the extracellular matrix and is important for the maintenance of tissue architecture. Depolymer ization of hyaluronic acid may facilitate tumor invasion. In addition, oligosaccharides of hyaluronic acid have been reported to induce angi ogenesis. We report here that a hyaluronidase similar to the one on hu man sperm is expressed by metastatic human melanoma, colon carcinoma, and glioblastoma cell lines and bg tumor biopsies from patients with c olorectal carcinomas, but not by tissues from normal colon. Moreover, angiogenesis is induced by hyaluronidase(+) tumor cells but not hyalur onidase(-) tumor cells and can be blocked by an inhibitor of hyaluroni dase. Tumor cells thus use hyaluronidase as one of the ''molecular sab oteurs') to depolymerize hyaluronic acid to facilitate invasion. As a consequence, breakdown products of hyaluronic acid can further promote tumor establishment by inducing angiogenesis. Hyaluronidase on tumor cells may provide a target for anti-neoplastic drugs.