20-HYDROXYEICOSATETRAENOIC ACID (20-HETE) PROMOTES A MALIGNANT PHENOTYPE IN HUMAN CASTRATION-RESISTANT PROSTATE CANCER CELLS THROUGH STIMULATION OF THE G PROTEIN-COUPLED RECEPTOR GPR75.

COLOMBERO C; FALCK J; CARDENAS S; DAKARAPU R; NOWICKI S.; PANELLO LC; COSTAS MA

Buenos Aires

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

20-Hydroxyeicosatetraenoic acid (20-HETE), the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to assess in vitro if 20-HETE/GPR75 modify the metastatic features of PC-3 cells.Cells were incubated with 20-HETE or its stable analog 5,14-HEDGE (both 0.1 nM) in the presence or absence of two different antagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or 10 uM). The following assays were performed: E-cadherin and Vimentin protein expression (epithelial-mesenchymal transition), zymography (release of matrix metalloproteinase-2 (MMP-2)), immunofluorescence and p-FAK (changes of cytoskeleton), scratch wound healing (migration), and soft agar colony formation (anchorage-independent growth). Results were analyzed using one-way ANOVA followed by Dunnet?s. 20-HETE (24h) increased by 150% the expression of vimentin (p