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Departments of Radiation Oncology [D. N., T. G., K. T., K. V. H.], Urology [G. G. H.], and Pathology [C. P., D. J. G., K. V. H.], Wayne State University School of Medicine, Detroit, Michigan 48202
Previously, we found a positive correlation between the expression of platelet-type 12-lipoxygenase (12-LOX) and the progression of human prostate adenocarcinoma (PCa; Gao et al., Urology, 46: 227237, 1995). To determine the role of 12-LOX in PCa progression, we generated stable 12-LOX-transfected PC3 cells, which synthesize high levels of 12-LOX protein and 12(S)-hydroxyeicosatetraenoic acid metabolite. In vitro, 12-LOX-transfected PC3 cells demonstrated a proliferation rate similar to neo controls. However, following s.c. injection into athymic nude mice, 12-LOX-transfected PC3 cells formed larger tumors than did the controls. Decreased necrosis and increased vascularization were observed in the tumors from 12-LOX-transfected PC3 cells. Both endothelial cell migration and Matrigel implantation assays indicate that 12-LOX-transfected PC3 cells were more angiogenic than their neo controls. These data indicate that 12-LOX stimulates human PCa tumor growth by a novel angiogenic mechanism.
1 This work was supported by NIH CA 29997, United States Army Prostate Cancer Research Program DAMD 17-98-1-8502, and the Harper Hospital Development Fund (to K. V. H.), D. N. was supported by a fellowship from the Cancer Research Foundation of American.
2 To whom requests for reprints should be addressed, at Department of Radiation Oncology, 431 Chemistry Building, Wayne State University, Detroit, MI 48202. Phone: (313) 577-1018; Fax: (313) 577-0798.
Received 5/20/98. Accepted 7/30/98.
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