Leung, Edmund, McArthur, David, Morris, A. G. (Alan George) and Williams, Nigel (2008) Cyclooxygenase-2 inhibition prevents migration of colorectal cancer cells to extracellular matrix by down-regulation of matrix metalloproteinase-2 expression. In: Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons, Seattle, WA, Jun 03-07, 2006. Published in: Diseases of the Colon and Rectum, Vol.51 (No.3). pp. 342-347.

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Abstract

Purpose: Matrix metalloproteinases-2 hydrolyses gelatins and collagens. It has many biologic functions, including cancer cells invasion. Overexpression of cyclooxygenase-2 is known to be involved in colorectal carcinogenesis, although the mechanism is unclear. Up-regulation of matrix metalloproteinases-2 expression may be one of the mechanisms, which explains how cyclooxygenase-2 expression promotes migration of colorectal cancer cells to extracellular matrix. Methods: Colorectal cancer cell lines HT29, CaCO2, and Colo205 were used. By using flow cytometry, their cyclooxygenase-2 expression was determined. These cell lines were modulated with NS398, a selective cyclooxygenase-2-inhibitor, and prostaglandin-E2. Western blot and enzyme-linked inmmunosorbent assay were used to determine these cells' matrix metalloproteinases-2 expression. These cell lines' ability to migrate into extracellular matrix was determined by Matrigel (R) (Millipore, Watford, UK) Invasion Chamber. Results: HT29 expressed more cyclooxygenase-2 than CaCO2. Cyclooxygenase-2 was not detected in Colo205. Matrix metalloproteinases-2 expression is highest in HT29 and least in Colo205. Cyclooxygenase-2 inhibition by NS398 showed decreased matrix metalloproteinases-2 expression in HT29 and CaCO2, but not Colo205, reversible with prostaglandin-E2. Prostaglandin-E2 was shown to up-regulate matrix metalloproteinases-2 expression in all cell lines. Matrigel (R) Invasion Chamber demonstrated that many more HT29 cells migrate across the membrane than CaCO2 and Colo205, and cyclooxygenase-2 inhibition reduced cellular migration in the cyclooxygenase-2-positive cell lines. Prostaglandin-E2 promoted migration in all cell lines. Conclusions: There is a positive relationship between cyclooxygenase-2 and matrix metalloproteinases-2 expression. The latter is modulated by prostaglandin-E2 in all cell lines and NS398 in cyclooxygenase-2-positive cells. Such modulation has a knock-on effect to the cells' ability to invade into extracellular matrix. Cyclooxygenase-2 and matrix metalloproteinases-2 expression are potential therapeutic targets into prevention of colorectal cancer metastasis.

Item Type:	Conference Item (UNSPECIFIED)
Subjects:	R Medicine > RC Internal medicine R Medicine > RD Surgery
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Diseases of the Colon and Rectum
Publisher:	Lippincott Williams & Wilkins
ISSN:	0012-3706
Date:	March 2008
Volume:	Vol.51
Number:	No.3
Number of Pages:	6
Page Range:	pp. 342-347
Identification Number:	10.1007/s10350-007-9120-4
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Title of Event:	Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons
Type of Event:	Conference
Location of Event:	Seattle, WA
Date(s) of Event:	Jun 03-07, 2006
URI:	http://wrap.warwick.ac.uk/id/eprint/30513

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