Expression of hyaluronidase by tumor cells induces angiogenesis in vivo

Dacai Liu, Eric Pearlman, Eugenia Diaconu, Kun Guo, Hiroshi Mori, Tariq Haqqi, Sanford Markowitz, James Willson, Man Sun Sy

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203 Scopus citations


Hyaluronic acid is a proteoglycan present in the extracellular matrix and is important for the maintenance of tissue architecture. Depolymerization of hyaluronic acid may facilitate tumor invasion. In addition, oligosaccharides of hyaluronic acid have been reported to induce angiogenesis. We report here that a hyaluronidase similar to the one on human sperm is expressed by metastatic human melanoma, colon carcinoma, and glioblastoma cell lines and by tumor biopsies from patients with colorectal carcinomas, but not by tissues from normal colon. Moreover, angiogenesis is induced by hyaluronidase+ tumor cells but not hyaluronidase- tumor cells and can be blocked by an inhibitor of hyaluronidase. Tumor cells thus use hyaluronidase as one of the 'molecular saboteurs' 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.

Original languageEnglish (US)
Pages (from-to)7832-7837
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Jul 23 1996

ASJC Scopus subject areas

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