Specific components of prostanoid-signaling pathways are present in non-small cell lung cancer cells.
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.
Kreutzer
Mihaela
M
Institute of Molecular Biology and Tumor Research (IMT), Philipps University, D-35032 Marburg, Germany.
Fauti
Tanja
T
Kaddatz
Kerstin
K
Seifart
Carola
C
Neubauer
Andreas
A
Schweer
Horst
H
Kömhoff
Martin
M
Müller-Brüsselbach
Sabine
S
Müller
Rolf
R
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D041681:NIH 3T3 Cells; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics* / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000378:metabolism
C545635:PTGER1 protein, human; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D011453:Prostaglandins; C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D015232:Dinoprostone