Pancreatic stellate cells (PSCs) express cyclooxygenase-2 (COX-2) and pancreatic cancer stimulates COX-2 in PSCs.
BACKGROUND
Cyclooxygenase 2 (COX-2), the inducible form of prostaglandin G/H synthase, is associated with several human cancers including pancreatic adenocarcinoma. Pancreatic stellate cells (PSCs) play a central role in the intense desmoplasia that surrounds pancreatic adenocarcinoma. The present study examined COX-2 expression in PSCs. PSCs isolated from normal rats, were cultured and exposed to conditioned medium (CM) from the human pancreatic cell line, PANC-1.


METHODS
COX-2 expression was evaluated by immunostaining and western blotting. Proliferation of PSCs was determined by thymidine incorporation and cell counting.


RESULTS
COX-2 was found to be constitutively expressed in PSCs, and COX-2 protein was up-regulated by PANC-1 CM. Moreover, the induction of COX-2 by PANC-1 CM was prevented by U0126, an extracellular signal-regulated kinase (ERK) 1/2 inhibitor suggesting that activation of ERK 1/2 is needed for stimulation of COX-2. Finally, NS398, a selective COX-2 inhibitor, reduced the growth of PSCs by PANC-1 CM, indicating that activation of COX-2 is required for cancer stimulated PSC proliferation.


CONCLUSIONS
The results suggest that COX-2 may play an important role in the regulation of PSC proliferation in response to pancreatic cancer.
Yoshida
Seiya
S
Department of Surgery, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 333 East Superior 4-713, Chicago, IL 60611, USA. yansei@jf7.so-net.ne.jp
Ujiki
Michael
M
Ding
Xian-Zhong
XZ
Pelham
Carolyn
C
Talamonti
Mark S
MS
Bell
Richard H
RH
Denham
Woody
W
Adrian
Thomas E
TE
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000201:enzymology*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
D002070:Butadienes; D017077:Culture Media, Conditioned; D052246:Cyclooxygenase 2 Inhibitors; D009570:Nitriles; D009578:Nitrobenzenes; D013449:Sulfonamides; C113580:U 0126; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2