Matrilysin in early stage intestinal tumorigenesis

Barbara M. Fingleton, Kathleen J. Heppner Goss, Howard C. Crawford, Lynn M. Matrisian

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The demonstration that matrix metalloproteinases [MMPs] play an active role in the invasion and metastasis stages of tumor progression has led to the development of a new class of anti-metastatic chemotherapeutic agent, the matrix metalloproteinase inhibitors [MMPIs]. We present evidence to suggest that the MMP matrilysin, in particular, plays an essential role in much earlier stages of intestinal tumorigenesis. Matrilysin is detected in a high percentage of pre-invasive lesions, in contrast to its absence in most normal tissues, and is expressed by the epithelial-derived tumor cells. Manipulating levels of this enzyme in vitro results in cell lines with enhanced tumorigenic potential, while ablating the gene in vivo leads to a significant reduction in tumor number in two different animal models of intestinal tumorigenesis. Additionally, regulation of matrilysin gene expression appears to be under the control of genetic pathways which are activated very early in the tumor development sequence. Although the precise mechanism by which matrilysin activity contributes to tumor formation is not yet clear, we propose that MMPIs may be of benefit as chemopreventative agents in addition to their therapeutic potential for metastatic disease.

Original languageEnglish (US)
Pages (from-to)102-110
Number of pages9
JournalAPMIS
Volume107
Issue number1
StatePublished - 1999
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 7
Carcinogenesis
Matrix Metalloproteinase Inhibitors
Neoplasms
Matrix Metalloproteinases
Gene Expression Regulation
Animal Models
Neoplasm Metastasis
Cell Line
Enzymes
Genes

Keywords

  • Animal models
  • APC; β-catenin
  • Colon cancer
  • Matrilysin
  • Min

ASJC Scopus subject areas

  • Immunology
  • Microbiology (medical)
  • Pathology and Forensic Medicine

Cite this

Fingleton, B. M., Heppner Goss, K. J., Crawford, H. C., & Matrisian, L. M. (1999). Matrilysin in early stage intestinal tumorigenesis. APMIS, 107(1), 102-110.

Matrilysin in early stage intestinal tumorigenesis. / Fingleton, Barbara M.; Heppner Goss, Kathleen J.; Crawford, Howard C.; Matrisian, Lynn M.

In: APMIS, Vol. 107, No. 1, 1999, p. 102-110.

Research output: Contribution to journalArticle

Fingleton, BM, Heppner Goss, KJ, Crawford, HC & Matrisian, LM 1999, 'Matrilysin in early stage intestinal tumorigenesis', APMIS, vol. 107, no. 1, pp. 102-110.
Fingleton BM, Heppner Goss KJ, Crawford HC, Matrisian LM. Matrilysin in early stage intestinal tumorigenesis. APMIS. 1999;107(1):102-110.
Fingleton, Barbara M. ; Heppner Goss, Kathleen J. ; Crawford, Howard C. ; Matrisian, Lynn M. / Matrilysin in early stage intestinal tumorigenesis. In: APMIS. 1999 ; Vol. 107, No. 1. pp. 102-110.
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