Hypoxia increases heparanase-dependent tumor cell invasion, which can be inhibited by antiheparanase antibodies

The beta-endoglucuronidase heparanase plays an important role in tumor invasion, a process that is significantly enhanced by hypoxia. We have used a strategy of stable transfection with antisense to derive ovarian carcinoma cell lines that express different levels of heparanase and used these to dem...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-06, Vol.64 (11), p.3928-3933
Main Authors: XIAOTONG HE, BRENCHLEY, Paul E. C, JAYSON, Gordon C, HAMPSON, Lynne, DAVIES, John, HAMPSON, Ian N
Format: Article
Language:English
Subjects:
Antibodies - immunology
Antibodies - pharmacology
Antineoplastic agents
Biological and medical sciences
Cell Hypoxia - physiology
Cell Line, Tumor
DNA, Antisense - genetics
Enzyme Activation
Female
Glucuronidase - antagonists & inhibitors
Glucuronidase - genetics
Glucuronidase - immunology
Glucuronidase - metabolism
Humans
Medical sciences
Neoplasm Invasiveness
Ovarian Neoplasms - enzymology
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Oxygen - metabolism
Oxygen - pharmacology
Pharmacology. Drug treatments
Transfection
Tumors
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Summary:The beta-endoglucuronidase heparanase plays an important role in tumor invasion, a process that is significantly enhanced by hypoxia. We have used a strategy of stable transfection with antisense to derive ovarian carcinoma cell lines that express different levels of heparanase and used these to demonstrate that invasion correlates with heparanase activity. Secreted heparanase activity was increased by reduction, hypoxia, and growth of cells under reduced oxygen (1%) augmented heparanase activity and invasion, both of which are inhibited by treatment with antiheparanase antibodies. This is the first demonstration that heparanase activity may be regulated by microenvironmental redox conditions, which influence invasion, and that invasion can be blocked with specific heparanase-neutralizing antibodies.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-2718