Yonsei Med J.  2010 Sep;51(5):692-699. 10.3349/ymj.2010.51.5.692.

Impacts of Cytosolic Phospholipase A2, 15-Prostaglandin Dehydrogenase, and Cyclooxygenase-2 Expressions on Tumor Progression in Colorectal Cancer

• Lim SC
• Cho H
• Lee TB
• Choi CH
• Min YD
• Kim SS
• Kim KJ

• KMID: 1071420
• DOI: http://doi.org/10.3349/ymj.2010.51.5.692

Abstract

PURPOSE
In addition to cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) have been suggested to be related to carcinogenesis of colorectal cancer (CRC). The aim of this study was to investigate the roles of cPLA2, COX-2, mPGES-1, and 15-PGDH in tumor progression.
MATERIALS AND METHODS
cPLA2, COX-2, mPGES-1, 15-PGDH, and vascular endothelial growth factor (VEGF) expressions were immunohistochemically examined in 89 CRC, and their expressions were compared with each other or clinicopathologic parameters as well as VEGF as tumor progression parameters.
RESULTS
cPLA2 was expressed in 54.5%, COX-2 in 80.5%, mPGES-1 in 96.4%, 15-PGDH in 46.1%, and VEGF in 65.9%. The expression of cPLA2 correlated with VEGF expression. COX-2 expression was correlated with the depth of invasion, tumor stage, cPLA2, and VEGF expressions. Moreover, VEGF revealed the highest expression in the tissues positive for both cPLA2 and COX-2. Furthermore, 15-PGDH expression was inversely correlated with VEGF expression.
CONCLUSION
The present study demonstrates that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression.

Keyword

cPLA2; COX-2; mPGES-1; 15-PGDH; colorectal cancer

MeSH Terms

Aged
Colorectal Neoplasms/*enzymology
Cyclooxygenase 2/*metabolism
Female
*Gene Expression Regulation, Enzymologic
Group IV Phospholipases A2/*metabolism
Humans
Hydroxyprostaglandin Dehydrogenases/*metabolism
Immunohistochemistry
Intramolecular Oxidoreductases/metabolism
Male
Middle Aged

Figure

• 

  Fig. 1 Immunohistochemical staining. (A) positive cPLA2 in tumor tissue. (B) Positive COX-2 in tumor tissue. (C) Positive mPGES-2 in tumor tissue. (D) Positive 15-PGDH in normal colonic epithelium. (E) Negative 15-PGDH in tumor tissue. (F) Positive VEGF in tumor tissue. cPLA2, cytosolic phospholipase A2; COX-2, cyclooxygenase 2; mPGES-2, microsomal prostaglandin E synthase-2; PGDH, prostaglandin dehydrogenase; VEGF, vascular endothelial growth factor.

• 

  Fig. 2 Relationship between COX-2 and cPLA2 expression in colorectal cancer (n = 79, r = 0.339, p = 0.002). COX-2, cyclooxygenase 2; cPLA2, cytosolic phospholipase A2.

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