Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer.

Abstract

BACKGROUND:

Patients with long-term ulcerative colitis are at risk for developing colorectal cancer.

METHODS:

Archival formalin-fixed paraffin-embedded tissue from ulcerative colitis patients who underwent a colectomy for high-grade dysplasia or carcinoma was examined for changes in expression of plasminogen activator inhibitor-1 (PAI-1) as well as other mediators of inflammation-associated cancer. Epithelia from areas of colons that showed histologic evidence of carcinoma, high-grade dysplasia, and epithelia that were not dysplastic or malignant but did contain evidence of prior inflammation (quiescent colitis) was microdissected using laser capture microscopy. mRNA was extracted from the microdissected tissue and PCR array analysis was performed. To extend our findings, PAI-1 protein levels were determined using immunohistochemistry.

RESULTS:

The mRNA expression of PAI-1 is increased 6-fold (p=0.02) when comparing the carcinoma group to the quiescent colitis group; increases were also observed in NFKB2, REL, SRC, and VEGFA. The protein levels of PAI-1 are increased by 50% (p<0.001) in high-grade dysplasia and by 60% (p<0.001) in carcinoma when compared to the quiescent colitis group.

CONCLUSIONS:

The increase in PAI-1 in high-grade dysplasia and carcinoma suggests a functional role for PAI-1 in malignant transformation in colitis-associated cancer. PAI-1 could also prove a useful diagnostic marker to identify patients at risk for neoplasia and it may be a useful therapeutic target to treat colitis-associated cancer.

• Authors: Earl Gillespie, Susan E Leeman, Luisa A Watts, Jennifer A Coukos, Michael J O'Brien, Sandra R Cerda, Francis A Farraye, Arthur F Stucchi
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 7 Issue 5 Pg. 403-11 (Jun 2013) ISSN: 1876-4479 [Electronic] England
• PMID: 22921465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B p52 Subunit
• NFKB2 protein, human
• Plasminogen Activator Inhibitor 1
• Proto-Oncogene Proteins c-rel
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• Proto-Oncogene Proteins pp60(c-src)

Topics

• Carcinoma (etiology, genetics, metabolism)
• Colitis, Ulcerative (complications)
• Colon (metabolism, pathology)
• Colonic Neoplasms (etiology, genetics, metabolism)
• Epithelial Cells (metabolism)
• Gene Expression
• Humans
• NF-kappa B p52 Subunit (genetics)
• Plasminogen Activator Inhibitor 1 (genetics, metabolism)
• Proto-Oncogene Proteins c-rel (genetics)
• Proto-Oncogene Proteins pp60(c-src) (genetics)
• RNA, Messenger (metabolism)
• Vascular Endothelial Growth Factor A (genetics)