PRODUCTION OF 13-HYDROXYOCTADECADIENOIC ACID (13-HODE) BY PROSTATE TUMORS AND CELL-LINES

The major lipoxygenation product derived from linoleic acid, 13-(S)-hy droxyoctadecadienoic acid (13-HODE), has been shown to be involved in cell proliferation and differentiation in a number of systems. Rapid d etection of picogram amounts of this bioactive lipid in biological sam ples, however, has been hindered due to lack of immunological reagents . In the current report, we have used a polyclonal antibody specific f or 13-(S)-HODE to detect this bioactive lipid for the first time in hu man prostate adenocarcinoma specimens (PCa) and the prostate cancer ce ll lines LNCaP and PC-3 by enzyme immunoassay. In addition, we have ve rified the quantitation of 13-HODE by chiral-phase HPLC and examined t he levels of lipoxygenase expression by Western, Northern, and RT-PCR analysis. Immunohistochemically detectable 13-HODE was observed in hum an PCa, whereas adjacent normal tissue showed no immunoreactivity. The presence of 15-lipoxygenase was evident by Western and RT-PCR analysi s in both LNCaP and PC-3 cells, while Northern blot analysis showed th e presence of 15-lipoxygenase message in LNCaP cells but failed to det ect any 15-lipoxygenase message in PC-3 cells. In contrast, quantitati on of 13-HODE by enzyme immunoassay and chiral-phase HPLC showed signi ficant levels of the compound in PC-3 cells but minimal enzymatically produced 13-HODE in LNCaP cells. These data provide a link between lin oleic acid metabolism and the development or progression of prostate c ancer. (C) 1997 Academic Press.