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Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin.

Publication ,  Journal Article
Wilson, CL; Heppner, KJ; Labosky, PA; Hogan, BL; Matrisian, LM
Published in: Proc Natl Acad Sci U S A
February 18, 1997

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 ApcMin 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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 18, 1997

Volume

94

Issue

4

Start / End Page

1402 / 1407

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Stem Cells
  • Phenotype
  • Mutagenesis, Site-Directed
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7
  • In Situ Hybridization
 

Citation

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Wilson, C. L., Heppner, K. J., Labosky, P. A., Hogan, B. L., & Matrisian, L. M. (1997). Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A, 94(4), 1402–1407. https://doi.org/10.1073/pnas.94.4.1402
Wilson, C. L., K. J. Heppner, P. A. Labosky, B. L. Hogan, and L. M. Matrisian. “Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin.Proc Natl Acad Sci U S A 94, no. 4 (February 18, 1997): 1402–7. https://doi.org/10.1073/pnas.94.4.1402.
Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1402–7.
Wilson, C. L., et al. “Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin.Proc Natl Acad Sci U S A, vol. 94, no. 4, Feb. 1997, pp. 1402–07. Pubmed, doi:10.1073/pnas.94.4.1402.
Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1402–1407.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 18, 1997

Volume

94

Issue

4

Start / End Page

1402 / 1407

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Stem Cells
  • Phenotype
  • Mutagenesis, Site-Directed
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7
  • In Situ Hybridization