Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth.
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: 227-237, 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.
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Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
Hillman
G G
GG
Geddes
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T
Tang
K
K
Pierson
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Grignon
D J
DJ
Honn
K V
KV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000502:physiology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D014162:Transfection
D009363:Neoplasm Proteins; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase