Reference SummaryWilson CL, Proc Natl Acad Sci U S A 1997 Feb 18;94(4):1402-7

Title

 Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin.

Authors

 Wilson CL; Heppner KJ; Labosky PA; Hogan BL; Matrisian LM

Journal

 Proc Natl Acad Sci U S A

Volume

 94

Issue

 4

Year

 1997

Pages

 1402-7

Abstract

 Matrix metalloproteinases (MMPs) classically have been implicated in basement membrane destruction associated with late-stage tumor cell invasion and metastasis. However, recent studies have demonstrated that one MMP family member, matrilysin, is expressed in a high percentage of early-stage human colorectal tumors, We analyzed matrilysin expression in benign intestinal tumors from mice heterozygous for the Apc(Min) allele (Min/+) and found that the mRNA was induced in the majority (88%) of these adenomas. Protein was detected in the tumor cells, where, surprisingly, it was predominantly immunolocalized to the lumenal surface of dysplastic glands rather than the basement membrane or extracellular matrix. To address the role of matrilysin in Min intestinal tumorigenesis, we generated Min/+ mice deficient in this MMP by gene targeting and homologous recombination, The absence of matrilysin resulted in a reduction in mean tumor multiplicity in Min/+ animals of approximately 60% and a significant decrease in the average tumor diameter. Based on these findings, we conclude that matrilysin is a suppressor of the Min phenotype, possibly by functioning in a capacity independent of matrix degradation, These results argue for the use of MMP inhibitors in the treatment and prevention of early-stage colon cancer.

Links

 J:38609 – MGI References
9037065 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6J-ApcMin/+ Expression of the wild type allele of the Mmp7 gene was reported to not be detected in the colon and small instestine of these mice
These mice were from The Jackson Laboratory.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma Intestine - Large Intestine - Colon

observed
C57BL/6J-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed
C57BL/6J-ApcMin/+ Intestine tumor Intestine

100
C57BL/6-ApcMin/+ Mmp7tm1Lmm Intestine tumor Intestine

100
C57BL/6-ApcMin/+ Mmp7tm1Lmm/+ Intestine tumor Intestine

100