Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas

Patrick A. Adegboyega, Omiyosoye Ololade, Jamal Saada, Randy Mifflin, John F. Di Mari, Don W. Powell

Research output: Contribution to journalArticle

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Abstract

Purpose: Recent data support the hypothesis that the inducible isoform of cyclooxygenase (COX-2) plays a role in the early stages of colonic carcinogenesis and that nonsteroidal anti-inflammatory drugs (NSAIDs) retard the development of colon cancer by modulating COX-2. However, the cell types responsible for producing COX-2 in colorectal adenomas remain a subject of controversy. Experimental Design: COX-2 expression in normal colonic mucosa (n = 50), hyperplastic polyps (n = 43), sporadic adenomas (n = 67), and invasive colonic adenocarcinoma (n = 39) was studied in formalin-fixed and paraffin-embedded tissue sections from endoscopy biopsy and colonic resection specimens. Immunohistochemistry (avidin-biotin complex technique with double immunolabeling) was used to identify the phenotypes of COX-2-producing cells. Results: In colorectal adenomas, increased expression of COX-2 was detected and localized to α smooth muscle actin (αSMA)-positive subepithelial stromal cells (myofibroblasts) in the periluminal region of the lamina propria in 63 (94%) of 67 cases. In contrast, in normal colonic mucosa and in hyperplastic polyps with intact epithelium, COX-2 expression was found only in macrophages and endothelial cells. In areas in which the surface epithelium was ulcerated in normal mucosa as well as hyperplastic or neoplastic polyps, COX-2 expression was increased in granulation tissue (and present in macrophages, endothelium, and myofibroblasts). In invasive carcinoma, COX-2 expression in myofibroblasts was limited to the adenomatous portion of the tumor and was detected in 62% of cases (n = 39). In addition, focal expression of COX-2 by malignant epithelial cells was observed in 23% of invasive adenocarcinoma. Conclusions: These results show that increased COX-2 expression in sporadic adenoma of the colon is common and is localized specifically to subepithelial intestinal myofibroblasts. These findings further support the hypothesis that myofibroblasts are important target cells for NSAID-mediated chemoprevention of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)5870-5879
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number17
DOIs
StatePublished - Sep 1 2004

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Myofibroblasts
Cyclooxygenase 2
Adenoma
Mucous Membrane
Polyps
Adenocarcinoma
Anti-Inflammatory Agents
Epithelium
Macrophages
Granulation Tissue
Avidin
Chemoprevention
Stromal Cells
Biotin
Pharmaceutical Preparations
Paraffin
Colonic Neoplasms
Formaldehyde
Endoscopy
Endothelium

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Adegboyega, P. A., Ololade, O., Saada, J., Mifflin, R., Di Mari, J. F., & Powell, D. W. (2004). Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas. Clinical Cancer Research, 10(17), 5870-5879. https://doi.org/10.1158/1078-0432.CCR-0431-03

Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas. / Adegboyega, Patrick A.; Ololade, Omiyosoye; Saada, Jamal; Mifflin, Randy; Di Mari, John F.; Powell, Don W.

In: Clinical Cancer Research, Vol. 10, No. 17, 01.09.2004, p. 5870-5879.

Research output: Contribution to journalArticle

Adegboyega, PA, Ololade, O, Saada, J, Mifflin, R, Di Mari, JF & Powell, DW 2004, 'Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas', Clinical Cancer Research, vol. 10, no. 17, pp. 5870-5879. https://doi.org/10.1158/1078-0432.CCR-0431-03
Adegboyega PA, Ololade O, Saada J, Mifflin R, Di Mari JF, Powell DW. Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas. Clinical Cancer Research. 2004 Sep 1;10(17):5870-5879. https://doi.org/10.1158/1078-0432.CCR-0431-03
Adegboyega, Patrick A. ; Ololade, Omiyosoye ; Saada, Jamal ; Mifflin, Randy ; Di Mari, John F. ; Powell, Don W. / Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 17. pp. 5870-5879.
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abstract = "Purpose: Recent data support the hypothesis that the inducible isoform of cyclooxygenase (COX-2) plays a role in the early stages of colonic carcinogenesis and that nonsteroidal anti-inflammatory drugs (NSAIDs) retard the development of colon cancer by modulating COX-2. However, the cell types responsible for producing COX-2 in colorectal adenomas remain a subject of controversy. Experimental Design: COX-2 expression in normal colonic mucosa (n = 50), hyperplastic polyps (n = 43), sporadic adenomas (n = 67), and invasive colonic adenocarcinoma (n = 39) was studied in formalin-fixed and paraffin-embedded tissue sections from endoscopy biopsy and colonic resection specimens. Immunohistochemistry (avidin-biotin complex technique with double immunolabeling) was used to identify the phenotypes of COX-2-producing cells. Results: In colorectal adenomas, increased expression of COX-2 was detected and localized to α smooth muscle actin (αSMA)-positive subepithelial stromal cells (myofibroblasts) in the periluminal region of the lamina propria in 63 (94{\%}) of 67 cases. In contrast, in normal colonic mucosa and in hyperplastic polyps with intact epithelium, COX-2 expression was found only in macrophages and endothelial cells. In areas in which the surface epithelium was ulcerated in normal mucosa as well as hyperplastic or neoplastic polyps, COX-2 expression was increased in granulation tissue (and present in macrophages, endothelium, and myofibroblasts). In invasive carcinoma, COX-2 expression in myofibroblasts was limited to the adenomatous portion of the tumor and was detected in 62{\%} of cases (n = 39). In addition, focal expression of COX-2 by malignant epithelial cells was observed in 23{\%} of invasive adenocarcinoma. Conclusions: These results show that increased COX-2 expression in sporadic adenoma of the colon is common and is localized specifically to subepithelial intestinal myofibroblasts. These findings further support the hypothesis that myofibroblasts are important target cells for NSAID-mediated chemoprevention of colorectal cancer.",
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