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. 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.
Liu
D
D
Institute of Pathology, Cancer Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Pearlman
E
E
Diaconu
E
E
Guo
K
K
Mori
H
H
Haqqi
T
T
Markowitz
S
S
Willson
J
J
Sy
M S
MS
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D020843:Chamomile; D003110:Colonic Neoplasms / Q000201:enzymology; D003315:Cornea; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005909:Glioblastoma / Q000201:enzymology; D005910:Glioma / Q000201:enzymology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008545:Melanoma / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D009822:Oils, Volatile / Q000494:pharmacology; D010946:Plants, Medicinal; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009822:Oils, Volatile; D012333:RNA, Messenger; D006821:Hyaluronoglucosaminidase