Expression and Tissue Localization of Matrix Metalloproteinase 7 (Matrilysin) in Human Gastric Carcinomas. Implications for Vessel Invasion and Metastasis

Int J Cancer. 1998 Apr 17;79(2):187-94. doi: 10.1002/(sici)1097-0215(19980417)79:2<187::aid-ijc15>3.0.co;2-7.

Abstract

We examined the production and tissue localization of matrix metalloproteinase-7 (MMP-7 = matrilysin) in human gastric carcinomas and analyzed the data in connection with the clinicopathological factors. Sandwich-enzyme immunoassay for the zymogen of MMP-7 (proMMP-7) showed enhanced production of MMP-7 in carcinoma tissues compared with control normal gastric mucosa. Immunohistochemical studies demonstrated that MMP-7 is localized predominantly to the carcinoma cells in 71% of the carcinoma samples (30/42 cases). The percentage of immunoreactive carcinoma cells to total carcinoma cells (positive ratio) was significantly higher in intestinal-type carcinomas (26%, median) than in diffuse-type carcinomas (3%, median) (p < 0.05). The positive ratio was markedly higher in carcinoma groups with vascular invasion (28%) or lymphatic permeation (12%) than in those without invasion (6%) or permeation (0%) (p < 0.05). It was also significantly higher in carcinoma groups with liver (49%) or lymph-node metastases (15%) than in those without metastases (6 and 2% respectively) (p < 0.05). Both proMMP-7 of 28 kDa and active MMP-7 of 19 kDa were detected in the carcinoma tissues by immunoblotting. Reverse-transcription-PCR showed specific amplification in 50% of the carcinoma cases (6/12 cases) and 8% of the normal control specimens (1/12 cases). In situ hybridization demonstrated that the carcinoma cells almost selectively express MMP-7 mRNA. These data suggest that enhanced production of proMMP-7 and its activation are implicated in invasion and metastasis of human gastric carcinomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Primers
  • Female
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / pathology
  • Humans
  • Immunoassay
  • Immunohistochemistry
  • In Situ Hybridization
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 7
  • Metalloendopeptidases / analysis
  • Metalloendopeptidases / biosynthesis*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Polymerase Chain Reaction
  • Prognosis
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery

Substances

  • DNA Primers
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7