Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's oesophageal adenocarcinoma

Br J Cancer. 2001 Aug 3;85(3):383-92. doi: 10.1054/bjoc.2001.1929.

Abstract

Oesophageal adenocarcinoma is believed to arise from metaplastic mucosa in the distal oesophagus, a condition also known as Barrett's oesophagus (BE). BE develops as a result of injury caused by refluxing gastric and duodenal contents and is associated with increased risk of malignant transformation. Matrix metalloproteinases (MMPs) have been implicated in all aspects of tumour progression; tumour growth, basement membrane degradation, invasion and metastatic spread. Using in situ hybridization, we investigated the expression patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metalloelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastases. Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-node metastases and its expression correlated with the histological aggressiveness of tumour. Matrilysin and metalloelastase were upregulated already in BE. Stromelysin-2 and collagenase-3 expression was detected only in a few tumours. Collagenase-1 was expressed by cancer and stromal cells in 9/15 tumours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 cancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectively. Laminin-5 and tenascin were abundantly expressed at the invasive front of poorly differentiated tumours, but not in BE. Our results indicate that matrilysin is the principal MMP expressed by tumour cells in oesophageal adenocarcinoma, and further studies are needed to investigate whether matrilysin or tenascin-C could be used as a predictive marker for progression of BE to cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Barrett Esophagus / enzymology*
  • Barrett Esophagus / pathology
  • Cell Adhesion Molecules / metabolism
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • In Situ Hybridization
  • Male
  • Matrix Metalloproteinase 12
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Middle Aged
  • RNA Probes
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • Tenascin / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism*
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Cell Adhesion Molecules
  • RNA Probes
  • RNA, Messenger
  • RNA, Neoplasm
  • Tenascin
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-3
  • kalinin
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7
  • MMP12 protein, human
  • Matrix Metalloproteinase 12