Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential

The involvement of 12-lipoxygenase (12-LOX) expression and function in tumo r metastasis has been demonstrated in several murine tumor cell lines. In a ddition, 12-LOX expression was detected in human prostatic tumors and corre lated to the clinical stage of disease. Here we provide data that human pro state cancer cell lines express the platelet-type isoform of 12-LOX at both the mRNA and protein levels, and immunohistochemistry revealed 12-LOX expr ession in human prostate tumors. The enzyme was localized to the plasma mem brane, cytoplasmic organelles and nucleus in non-metastatic cells (PC-3 nm) and to the cytoskeleton and nucleus in metastatic cells (DU-145). After or thotopic/intraprostatic injection of tumor cells into SCID mice, the metast atic prostate carcinoma cells (DU-145) expressed 12-LOX at a significantly higher level compared with the non-metastatic counterparts, PC-3nm. The fun ctional involvement of 12-LOX in the metastatic process was demonstrated wh en DU-145 cells were pretreated in vitro with the 12-LOX inhibitors N-benzy l-N-hydroxy-5-phenylpentamide (BHPP) or baicalein, the use of which signifi cantly inhibited lung colonization. These data suggest a potential involvem ent of 12-LOX in the progression of human prostate cancer. Int. J. Cancer 8 7: 37-43, 2000. (C) 2000 Wiley-Liss. Inc.