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

COX-2 expression was evaluated by immunostaining and western blotting. Proliferation of PSCs was determined by thymidine incorporation and cell counting.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.The results suggest that COX-2 may play an important role in the regulation of PSC proliferation in response to pancreatic cancer.Vitamin A-containing cells were first reported in 1982 by Watari et al. in vitamin A loaded mice using fluorescence and electron microscopy [1]. This cell type was subsequently identified by electron microscopy in normal rat and human pancreatic tissues [2]. These cells were identified as pancreatic stellate cells (PSCs) by Apte et al and Bachem et al in 1998 [3,4]. In the normal pancreas, stellate cells are quiescent and can be identified by the presence of vitamin A-containing lipid droplets in the cytoplasm. In response to pancreatic injury or inflammation, PSCs are transformed ("activated") from quiescent phenotypes into highly proliferative myofibroblast-like cells which express the cytoskeletal protein α-smooth muscle actin (α-SMA), and produce type I collagen and other extracellular matrix components. Many of the morphological and metabolic changes associated with the activation of PSCs in animal models of fibrosis also occur when these cells are cultured on plastic in serum-containing medium.Activated PSCs have also been implicated in the deposition of extracellular matrix components in pancreatic adenocarcinoma [5]. In patients with pancreatic cancer, an intense, interstitial, fibrillar staining for PSCs