Regulation of cathepsin B and L expression in vitro in gastric cancer tissues by egg cystatin

J Exp Ther Oncol. 2003 Nov-Dec;3(6):319-24. doi: 10.1111/j.1533-869x.2003.01105.x.

Abstract

Background: Degradation of the basement membrane and surrounding extracellular matrix is likely to represent a key step in cancer invasion and metastasis. The purpose of this study was to determine whether gastric cancer tissues demonstrate higher cysteine proteases activities: cathepsins B and L during cancer progression in compression with non-cancerous tissues.

Methods: We measured the expression of both cathepsins B and L in 30 patients with gastric cancer tissues and non-cancerous tissues activities by a fluorescence assay and immunohistochemical staining. We attempted to regulate cathepsin B and L expression using egg white cystatin.

Results: The activities of cathepsins B and L were significantly higher in cancerous than in non-cancerous tissues (P </= 0.0001). Activities of these enzymes decreased 18-fold after treatment of tissue homogenates with 5 nM of purified egg white cystatin. Immunohistochemical staining was significant and positive expression of low molecular weight cystatin was observed on the tumor cell surface in gastric carcinoma. It was found that non-cancerous tissues (control) were not stained with anti-egg white antibody.

Conclusion: Our experiment demonstrated that the cysteine peptidases cathepsins B and L may be useful for the early detection of gastric cancer. The results suggest that addition of egg white cystatin reduces the activities of cathepsins B and L to that of non-cancerous values.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Cathepsin B / drug effects
  • Cathepsin B / metabolism*
  • Cathepsin L
  • Cathepsins / drug effects
  • Cathepsins / metabolism*
  • Cystatins / pharmacology*
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • Cystatins
  • Cysteine Proteinase Inhibitors
  • cystatin, egg-white
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L