Cyclooxygenase-2 Expression and Angiogenesis in Gastric Hyperplastic Polyp – Association with Polyp Size

Abstract

Background: Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin synthesis, and plays an important role in tumor enlargement. COX-2 is expressed in human gastric and colorectal tumors, and the expression increases in a tumor size-dependent manner. In the present study, we attempted to examine the COX-2 expression pattern in gastric hyperplastic polyp, a non-tumorous lesion. Patients and Methods: Fifty-eight gastric hyperplastic polyps, obtained by endoscopic polypectomy, were immunostained with anti-COX-2 and antivascular endothelial growth factor (VEGF) antibodies. Microvessel density (MVD) was determined by von Willebrand factor immunostaining. Results: In larger gastric hyperplastic polyps, COX-2 was expressed mainly on the luminal side of the polyp stroma, while it was absent in smaller polyps. A significant correlation between COX-2 immunoreactivity and polyp size was observed (p < 0.01). High VEGF expression and MVD were observed mainly in the same stromal region of the polyps where COX-2 was expressed. Both VEGF expression and MVD were also correlated with polyp size significantly (ps < 0.01). Conclusions: COX-2 expression increased in a size-dependent manner in non-tumorous hyperplastic polyps, suggesting that COX-2 expression is not necessarily linked to epithelial cell transformation. Moreover, COX-2 may participate in polyp enlargement through angiogenesis by promoting VEGF production.

Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway

“…However, the regulatory mechanisms of stromal COX-2 induction in the process of tumor formation are still largely unknown. In this regard, we previously demonstrated that stromal COX-2 expression is increased in a polyp size-dependent manner not only in Apc D716 mouse intestinal tumors but also in benign human gastric hyperplastic polyps (Seno et al, 2002;Kawada et al, 2003). These data imply a universal regulatory mechanism of COX-2 induction in the stromal cells regardless of the nature of the adjacent epithelial cells.…”

“…While considering such regulatory mechanisms of COX-2 induction, we noticed one of the common phenomena observed during the growth of intestinal adenomatous polyps and gastric hyperplastic polyps: the increase of epithelial cell number and density (Sonoshita et al, 2001;Preston et al, 2003;Boman et al, 2004). In addition, we are interested in the fact that COX-2 is expressed in the stromal cells that are not in direct contact with adjacent epithelial cells (Oshima et al, 1996;Chapple et al, 2002;Seno et al, 2002;Kawada et al, 2003). In the present study, therefore, we simulated such conditions in vitro, and examined the roles of the epithelial-mesenchymal interactions in COX-2 induction in stromal cells using our co-cultured model.…”

“…The regulatory mechanisms of COX-2 expression in those stromal cells in early-stage tumorigenesis are not fully understood (Hanahan and Folkman, 1996;Hoper et al, 1997;Masferrer et al, 2000;Williams et al, 2000;Chapple et al, 2002;Seno et al, 2002;Ricci et al, 2003). In this context, we previously showed that COX-2 was expressed in the stroma of gastric hyperplastic polyps as well, a benign polypoid lesion of the stomach (Kawada et al, 2003). Several studies have indicated that COX-2 expression is upregulated in proportion to the size of the tumors (Eberhart et al, 1994;Fujita et al, 1998;Seno et al, 2002), consistent with our previous report regarding benign gastric hyperplastic polyps (Kawada et al, 2003).…”

“…In this context, we previously showed that COX-2 was expressed in the stroma of gastric hyperplastic polyps as well, a benign polypoid lesion of the stomach (Kawada et al, 2003). Several studies have indicated that COX-2 expression is upregulated in proportion to the size of the tumors (Eberhart et al, 1994;Fujita et al, 1998;Seno et al, 2002), consistent with our previous report regarding benign gastric hyperplastic polyps (Kawada et al, 2003). Thus, a common regulatory mechanism of COX-2 expression appears to be present during neoplastic and non-neoplastic polyp development.…”

Current Concepts in Therapy of Chronic Rhinosinusitis and Nasal Polyposis

“…These findings need to be discussed with respect to the differential expression of COX-1 and -2 in nasal polyps, where COX-1 is up-and COX-2 is downregulated, following immunohistochemical analysis [18]. Studies involving intestinal hyperplastic polyps suggest that especially COX-1 can upregulate VPF/VEGF [19][20][21]. This mechanism might play a key role in polyp growth and heavy edema formation in nasal polyposis.…”