In vitro expression of genes encoding HIF1α, VEGFA, PGE2 synthases, and PGE2 receptors in feline oral squamous cell carcinoma.

Abstract

Feline oral squamous cell carcinoma (FOSCC) is an aggressive tumor with poor outcomes. Mechanisms of prostaglandin E2 (PGE2)-related inflammation and angiogenesis interact in human OSCC; however, this relationship has not been reported in FOSCC, to our knowledge. We aimed to characterize expression of genes encoding PGE2 synthases (PTGES1-3), PGE2 receptors (EP1-4), hypoxia inducible factor 1α (HIF1A), and vascular and endothelial growth factor A (VEGFA) in FOSCC cell lines (SCCF1-3) in vitro using reverse-transcription quantitative real-time PCR (RT-qPCR). Expression of PTGES1, PTGES3, EP4, and VEGFA were serum-inducible in SCCF2 cells; VEGFA was also inducible in SCCF1 cells (p ≤ 0.05). Compared to other serum-treated cells, SCCF3 cells had the lowest VEGFA expression despite the highest HIF1A (p ≤ 0.05) expression. PGE2 (5 µg/mL and 35 µg/mL) was added to SCCF2 cells for 4 different times (30, 60, 120, 240 min). Both doses of PGE2 stimulated expression of HIF1A and CD147 at 240 min (p ≤ 0.05). PGE2 treatment stimulated cyclooxygenase 2 (COX2) expression at 30 min, followed by suppression at 60 and 120 min and a sharp reduction in EP4 expression at 60 min (p ≤ 0.05). Treatment of SCCF2 with PGE2 and EP4 antagonist L-161,982 increased COX2 expression, and L-161,982 (alone and in combination with PGE2) stimulated EP4 expression (p ≤ 0.05). Genes for PGE2 synthase enzymes, PGE2 receptors, HIF1α and VEGFA were expressed in FOSCC cells in vitro. SCCF2 cells responded to exogenous PGE2 and EP4 antagonism, suggesting that EP4 activity in FOSCC deserves more study.