Specific components of prostanoid-signaling pathways are present in non-small cell lung cancer cells

Abstract

In the present study, we measured prostanoid synthesis and the expression of genes associated with prostanoid signaling in human non-small cell lung carcinoma (NSCLC) cell lines and in primary human tumors. Consistent with the proposed growth promoting role of PGE2, we found that NSCLC cell lines frequently co-expressed the genes encoding cyclooxygenase-2 and the prostaglandin E2 (PGE2) receptors EP1, 2 and 4 concomitant with the synthesis of PGE2. In contrast, NSCLC cells did not synthesize appreciable amounts of prostaglandin I2 (PGI2, prostacyclin), lacked PGI2 synthase (PGIS) and did not express the gene coding for the PGI2 receptor IP at detectable levels. In agreement with this finding, PGIS mRNA levels were dramatically diminished in primary human tumor samples as compared to matched normal lung tissue. Finally, thromboxane A2 (TxA2) was synthesized in NSCLC cell lines, but transcription of the gene coding for the TxA2 receptor TP was not observed in these cells. In marked contrast, lung fibroblasts synthesized all three prostanoids and their receptors at high levels. While the observed expression patterns were consistent with the existence of autocrine/paracrine PGE2 signaling loops in NSCLC cells, PGI2- and TxA2-mediated signals may play a role in tumor stroma cells.