Bioactive Lipids: Role in Prostate Cancer Angiogensis
Abstract
The hypothesis to be tested was that an increase in 12-lipoxygenase activity in prostate cancer cells would increase their angiogenic potential, either directly through the direct metabolite 12(S)-HETE or indirectly, through stimulation of angiogenic factors. The preliminary data regarding increased vascularization by 12-LOX transfectant PC-3 cells was confirmed in two additional PC-3 transfectants. In addition, we were able to demonstrate that 12(S)-HETE does stimulate endothelial cell migration. This stimulated migration occurred through activation of MAP kinase. We also determined that 12-LOX transfected cells secreted increased amounts of VEGF but not hFGF or IL8. Further studies demonstrated that 12(S)-HETE activated the VEGF promoter activity and we also confirmed increased VECF mRNA in 12-LOX transfectants by Northern blot. The role of increased VEGF production in 12-LOX transfectants was confirmed using a neutralizing antibody. The first four technical objectives have been met and work continues on technical objective five and six.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA384373
Entities
People
- Kenneth Honn
Organizations
- Wayne State University