胰腺星状细胞（PSCs）表达环氧合酶-2（COX-2），胰腺癌可刺激PSCs中的COX-2。

Pancreatic stellate cells (PSCs) express cyclooxygenase-2 (COX-2) and pancreatic cancer stimulates COX-2 in PSCs.

作者信息

Yoshida Seiya, Ujiki Michael, Ding Xian-Zhong, Pelham Carolyn, Talamonti Mark S, Bell Richard H, Denham Woody, Adrian Thomas E

机构信息

Department of Surgery, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 333 East Superior 4-713, Chicago, IL 60611, USA.

出版信息

Mol Cancer. 2005 Aug 5;4:27. doi: 10.1186/1476-4598-4-27.

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.

CONCLUSION

The results suggest that COX-2 may play an important role in the regulation of PSC proliferation in response to pancreatic cancer.

背景

环氧化酶2（COX-2）是前列腺素G/H合酶的诱导型，与包括胰腺腺癌在内的多种人类癌症相关。胰腺星状细胞（PSC）在围绕胰腺腺癌的强烈促结缔组织增生中起核心作用。本研究检测了PSC中COX-2的表达。从正常大鼠分离的PSC进行培养，并暴露于来自人胰腺细胞系PANC-1的条件培养基（CM）中。

方法

通过免疫染色和蛋白质印迹法评估COX-2的表达。通过胸腺嘧啶核苷掺入和细胞计数来测定PSC的增殖。

结果

发现COX-2在PSC中组成性表达，并且COX-2蛋白被PANC-1 CM上调。此外，细胞外信号调节激酶（ERK）1/2抑制剂U0126可阻止PANC-1 CM对COX-2的诱导，这表明ERK 1/2的激活是刺激COX-2所必需的。最后，选择性COX-2抑制剂NS398降低了PANC-1 CM对PSC生长的促进作用，表明COX-2的激活是癌症刺激PSC增殖所必需的。