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Molecular Angiogenesis Group, Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom [R. C., H-T. Z., R. B.], and Department of Pharmacology, University of Florence, Viale G. B. Morgagni 65, 50134 Florence, Italy [S. D., M. Z.]
Recent analysis of bladder tumors has correlated expression of the neurokine midkine (MK) with poor patient survival. To examine a role for MK and the related pleiotrophin (PTN) in tumorigenesis, they were overexpressed in MCF-7 breast carcinoma cells. Expression had no effect on in vitro growth but conferred a growth advantage in vivo. Enhanced tumor growth correlated with increased vascular density and endothelial proliferation, implicating an angiogenic role for MK and PTN. Angiogenic activity of MK and PTN was confirmed in the rabbit corneal assay. Our data therefore identify two novel targets for antiangiogenic drug development.
1 Supported by the European Communities BIOMED-2: Angiogenesis and Cancer, the Italian Association for Cancer Research, and the National Research Council of Italy.
2 To whom requests for reprints should be addressed. Phone: 44-1865-222421; Fax: 44-1865-222431.
Received 10/23/96. Accepted 3/ 8/97.
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