Reference SummaryGuillen-Ahlers H, Carcinogenesis 2008 Jul;29(7):1421-7

Title

Sulindac treatment alters collagen and matrilysin expression in adenomas of ApcMin/+ mice.

Authors

Guillen-Ahlers H; Buechler SA; Suckow MA; Castellino FJ; Ploplis VA

Journal

Carcinogenesis

Volume

Issue

Year

2008

Pages

1421-7

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown potential as chemopreventive agents against cancer formation, especially colorectal cancers. However, the mechanisms by which these drugs act are not fully understood. In this study, Apc(Min/+) mice, a genetic model of human familial adenomatous polyposis, were treated with sulindac, and these mice demonstrated tumor reduction of >80%, consistent with previous reports. Gene microarray analyses of RNA from adenoma-derived dysplastic epithelial cells revealed that collagen genes, viz. Col1a2, Col5a2, Col6a2 and Col6a3, were upregulated, and matrilysin matrix metalloproteases-7 (Mmp7) was downregulated, in sulindac-treated mice. Reverse transcription-polymerase chain reaction validated gene expression of the Col6a2 subunit of collagen VI and of Mmp7. Confocal microscopy and immunofluorescence showed that within the tumors of non-treated mice, collagen VI was present in low amounts, but was enhanced within the tumors of sulindac-treated mice. Collagens I and V demonstrated similar patterns, but were not as prominent as collagen VI. Mmp7 was found in 'hot spot' areas within the tumors of Apc(Min/+) mice treated with the vehicle, but was greatly diminished in those mice treated with sulindac. Studies with Apc(Min/+)/Mmp7(-/-) double-deficient mice demonstrated the reciprocal relationships of Mmp7 expression and the levels of these three collagens in vivo. The results of this study demonstrated that sulindac was effective in increasing the expression of different collagens and decreasing the expression of Mmp7, effects that may contribute to altered tumor burden in cancer patients undergoing NSAIDs treatments.

Links

J:139063 – MGI References
18499699 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6J-Apc^Min/+ Mmp7^tm1Lmm	These mice were generated by crossing B6.129-Mmp7^tm1Lmm/J and C57BL/6J-Apc^Min/J mice (from the Jackson laboratory), and then crossing the F1 offspring.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C57BL/6J-Apc^Min/+	Intestine adenoma		Intestine	observed
C57BL/6J-Apc^Min/+	Intestine adenoma	sulindac	Intestine	observed
C57BL/6J-Apc^Min/+ Mmp7^tm1Lmm	Intestine adenoma		Intestine	observed