Abstract 1676: 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer

Abstract

Abstract Introduction 15-lipoxygenase-2 (15-LOX-2) is a lipid oxidizing enzyme which converts the unsaturated fatty acids (Arachidonic and linoleic acid) to bioactive lipids with anti-inflammatory properties. Abundantly expressed in normal prostate, 15-LOX-2 expression and activities were found reduced in prostate tumors. 15-LOX-2 has been suggested as functional tumor suppressor since restoration of its expression was found to reduce prostate tumor formation and growth and induce tumor dormancy. However, it is unknown how 15-LOX-2 modulates prostate tumor progression and metastasis. Methods Silico analyses of gene array data, Inducible Tet-on system to express 15-LOX-2 in PC3MM cells in an inducible manner, qPCR to check the expressions, western blot, wound healing assay, immunohistochemistry. Result Through in silico analyses of gene array data, we found 15-LOX-2 expression was markedly reduced in metastatic prostate tumors when compared to normal or primary prostate tumor tissues. To determine whether 15-LOX-2 can modulate metastatic potentials of prostate cancer, we used an Inducible Tet-on system to express 15-LOX-2 in PC3MM cells. Treatment with 750ng/ml of doxycycline led to induced expression of 15-LOX-2 in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells caused re-expression of several epithelial markers including claudin, desmocollin, desmoglein, Jam, EPCAM, β-Catenin molecules involved in the tight and desmosomal junctions. At mean time, 15-LOX-2 expression led to a decrease in the levels of mesenchymal markers, vitronectin and fibronectin, in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells reduced cell migration and reduced MMP2 and MMP3 expression. Conclusion Our data suggest that 15-LOX-2 is a barrier for prostate tumor cells to acquire metastatic potentials through inhibiting epithelial to mesenchymal transition. Citation Format: Rana K. Alfardan, Debasish Boral, Daotai Nie. 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1676.