Pancreatic Stellate Cells (PSCs) express Cyclooxygenase-2 (COX-2) and pancreatic cancer stimulates COX-2 in PSCs

<p>Abstract</p> <p>Background</p> <p>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...

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Bibliographic Details
Main Authors: Denham Woody, Bell Richard H, Talamonti Mark S, Pelham Carolyn, Ding Xian-Zhong, Ujiki Michael, Yoshida Seiya, Adrian Thomas E
Format: Article
Language:English
Published: BMC 2005-08-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/4/1/27
Description
Summary:<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>COX-2 expression was evaluated by immunostaining and western blotting. Proliferation of PSCs was determined by thymidine incorporation and cell counting.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>The results suggest that COX-2 may play an important role in the regulation of PSC proliferation in response to pancreatic cancer.</p>
ISSN:1476-4598