Cyclooxygenase-2 Expression Is Related to the Epithelial-to-Mesenchymal Transition in Human Colon Cancers.
10.3349/ymj.2009.50.6.818
- Author:
Tae Jung JANG
1
;
Kyu Ha JEON
;
Ki Hoon JUNG
Author Information
1. Department of Pathology, Dongguk University College of Medicine, Gyeongju, Korea. taejung@mail.dongguk.ac.kr
- Publication Type:Original Article ; In Vitro
- Keywords:
Epithelial-to-mesenchymal transition;
COX-2;
E-cadherin;
Snail;
colon cancers
- MeSH:
Adult;
Aged;
Aged, 80 and over;
Blotting, Western;
Cadherins/genetics/metabolism;
Cell Differentiation/genetics/physiology;
Cell Line, Tumor;
Cell Movement/drug effects/genetics;
Colonic Neoplasms/*metabolism/*pathology;
Cyclooxygenase 2/genetics/metabolism/*physiology;
Dinoprostone/pharmacology;
Epithelial Cells/*cytology/metabolism;
Epithelium/*metabolism;
Female;
HT29 Cells;
Homeodomain Proteins/genetics/metabolism;
Humans;
Immunohistochemistry;
Male;
Mesoderm/*cytology/*metabolism;
Middle Aged;
Reverse Transcriptase Polymerase Chain Reaction;
Tetradecanoylphorbol Acetate/pharmacology;
Transcription Factors/genetics/metabolism
- From:Yonsei Medical Journal
2009;50(6):818-824
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Down-regulation of E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT). EMT progression in cancer cells is associated with the loss of certain epithelial markers and the acquisition of a mesenchymal phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis in colon cancer. This study investigated the relationship between E-cadherin and COX-2 in colon cancer cells and human colon tumors. MATERIALS AND METHODS: Colon cancer cell lines and immunohistochemistry were used. RESULTS: E-cadherin expression was inversely related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic expression of COX-2 or Snail reduced E-cadherin and induced a scattered, flattened phenotype with few intercellular contacts in colon cancer cells. Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase expression, and increased the cells' motility. In addition, exposure to prostaglandin E2 increased Snail expression and cell motility, and decreased E-cadherin expression. Membranous E-cadherin expression was lower in adenomas and cancers than in the adjacent, non-neoplastic epithelium. In contrast, the expressions of Snail and COX-2 were higher in cancers than in normal tissues and adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E-cadherin expression. Moreover, COX-2 expression was related to higher tumor stages and was significantly higher in nodal metastatic lesions than primary cancers. CONCLUSION: This study suggests that COX-2 may have a role in tumor metastasis via EMT.
