Cathepsin B and glioma invasion

Int J Dev Neurosci. Aug-Oct 1999;17(5-6):483-94. doi: 10.1016/s0736-5748(99)00011-8.

Abstract

Increased expression of cathepsin B has been reported in a number of human and animal tumors. This has also been observed in human gliomas where increases in cathepsin B mRNA, protein, activity and secretion parallel malignant progression. In the present study, we showed that cathepsin B was directly involved in glioma cell invasion. Activity of cathepsin B was an order of magnitude higher in glioma tissue than in matched normal brain. Inhibitors of cysteine proteases reduced invasion of glioma cells in two in vitro models: invasion through Matrigel and infiltration of a glioma spheroid into a normal brain aggregate. Glioma spheroids expressed higher levels of cathepsin B than did monolayers and the ability of subclones differing in cathepsin B activity to infiltrate normal brain aggregates paralleled their cathepsin B activity. We confirmed that intracellular staining for cathepsin B occurs at the cell periphery and in cell processes and observed extracellular staining on the cell surface. In addition, we demonstrated that intracellular cathepsin B located at the cell periphery and in processes was active. The cell surface cathepsin B colocalized with areas of degradation of an extracellular matrix component. We hypothesize that the increased expression of active cathepsin B in gliomas leads to increases in invasion in vitro and in vivo and have developed a xenotransplant model in which this hypothesis can be tested.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cathepsin B / genetics*
  • Cell Line
  • Cysteine Proteinase Inhibitors / pharmacology
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Neoplasm Invasiveness
  • Rats
  • Reference Values
  • Transplantation, Heterologous

Substances

  • Cysteine Proteinase Inhibitors
  • Cathepsin B