PGE 2 Production in Oral Cancer Cell Lines is COX-2-dependent

Abstract

It has been suggested that epithelial cyclooxyge-nase-2 (COX-2) promotes oral carcinogenesis and carcinoma malignancy through increased prostaglandin E₂ (PGE₂) production. Although oral squamous cell carcinomas (OSCC) often express COX-2, they may also produce PGE₂ in a COX-1-dependent manner. We used 6 isolated cell lines to investigate which COX isoforms OSCC may use for PGE₂ production. COX-1 and -2 expression patterns divided the 6 OSCC cell lines into 3 distinct groups: both COX isoforms low, only COX-1 high, or both COX isoforms high. Multicolor immunohistofluorescence staining confirmed the COX-expression profiles in organotypic 3D cultures and the COX-2 dominance in OSCC tumors. Epidermal growth factor (EGF) stimulation induced COX-2 (but not COX-1) expression and increased PGE₂ production, which was attenuated by COX-2 (but not COX-1) specific inhibition or siRNA-mediated COX-2 gene knockdown. Thus, PGE₂ production in OSCC cell lines was COX-2-dependent.