Cyclooxygenase-2 expression is related to the epithelial-to-mesenchymal transition in human colon cancers.
OBJECTIVE
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.


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 E(2) 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.


CONCLUSIONS
This study suggests that COX-2 may have a role in tumor metastasis via EMT.
Jang
Tae Jung
TJ
Department of Pathology, Dongguk University College of Medicine, Gyeongju, Korea. taejung@mail.dongguk.ac.kr
Jeon
Kyu Ha
KH
Jung
Ki Hoon
KH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D018398:Homeodomain Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate