Article Text

Download PDFPDF
Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers
  1. Y Adachia,
  2. H Yamamotoa,
  3. F Itoha,
  4. Y Hinodaa,
  5. Y Okadab,
  6. K Imaia
  1. aFirst Department of Internal Medicine, Sapporo Medical University, Sapporo 060, Japan, bDepartment of Pathology, School of Medicine, Keio University, Tokyo 160, Japan
  1. Dr F Itoh, First Department of Internal Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo 060, Japan.

Abstract

BACKGROUND/AIM Matrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointestinal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers.

PATIENTS (SUBJECTS)/METHODS The relation between matrilysin expression and Dukes’s type was investigated immunohistochemically in 83 surgically resected colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of colon cancer cells transfected with matrilysin cDNA were examined after subcutaneous injection into SCID mice.

RESULTS In 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matrilysin correlated significantly with the presence of nodal or distant metastases (p<0.05). In addition, matrilysin transfectants formed invasive tumours and multiple liver metastases in SCID mice, without producing any significant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metastatic lesions (p<0.001).

CONCLUSIONS Matrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human colorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.

  • matrix metalloproteinase
  • matrilysin
  • MMP-7
  • colorectal cancer
  • metastasis
  • transfection
  • human
  • Abbreviations used in this paper

    MMP
    matrix metalloproteinase
    MT1-MMP
    membrane type-1 matrix metalloproteinase
    SDS
    sodium dodecyl sulphate
  • Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

  • Abbreviations used in this paper

    MMP
    matrix metalloproteinase
    MT1-MMP
    membrane type-1 matrix metalloproteinase
    SDS
    sodium dodecyl sulphate
  • View Full Text