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

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 t umour progression; tumour growth, basement membrane degradation, invasion a nd metastatic spread. Using in situ hybridization, we investigated the expr ession patterns of collagenases-1 and -3, stromelysin-2, matrilysin, metall oelastase and TIMPs-1 and -3 in BE, adenocarcinoma and lymph-node metastase s, Matrilysin was expressed abundantly in 12/15 tumours and in 4/6 lymph-no de metastases and its expression correlated with the histological aggressiv eness 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 tu mours. Tumour-infiltrating macrophages expressed metalloelastase in 13/15 c ancers. TIMPs-1 and -3 were expressed in 12/15 and 11/15 tumours, respectiv ely. 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 a denocarcinoma, and further studies are needed to investigate whether matril ysin or tenascin-C could be used as a predictive marker for progression of BE to cancer. (C) 2001 Cancer Research Campaign.