Altered intracellular processing and enhanced secretion of procathepsin D in a highly deviated rat hepatoma

Int J Cancer. 1995 Jan 3;60(1):61-4. doi: 10.1002/ijc.2910600109.

Abstract

Both freshly-isolated rat hepatocytes and Morris hepatoma 7777 cells synthesized cathepsin D as a precursor that was either processed intracellular to smaller mature forms or secreted into the medium. The pattern of mature enzyme forms was different in the 2 cell types. In addition, the relative amount of precursor secreted was much higher for hepatoma cells. Monensin strongly enhanced the secretion and also impaired the intracellular transport-linked maturation of procathepsin D in hepatocytes, while it markedly inhibited intracellular maturation and only slightly increased secretion of the pro-enzyme in hepatoma cells. Ammonium chloride influenced the intralysosomal segregation and maturation of procathepsin D in hepatocytes but not in hepatoma cells. Our observations indicate that (i) the lysosomal segregation of cathepsin D was less efficient and its fractional secretion higher in hepatoma cells than in hepatocytes; (ii) in the 2 cell types, delivery to lysosomes and processing of procathepsin D were differently sensitive to increases in the vacuolar pH.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin D / biosynthesis
  • Cathepsin D / metabolism*
  • Enzyme Precursors / biosynthesis
  • Enzyme Precursors / metabolism*
  • Hydrogen-Ion Concentration
  • Intracellular Fluid / metabolism
  • Liver / metabolism
  • Liver / ultrastructure
  • Liver Neoplasms, Experimental / metabolism*
  • Liver Neoplasms, Experimental / ultrastructure
  • Rats
  • Tumor Cells, Cultured
  • Vacuoles / metabolism

Substances

  • Enzyme Precursors
  • procathepsin D
  • Cathepsin D