Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells

Isabelle Hamer, Edouard Delaive, Marc Dieu, Fadi Abdul Sater, Ludovic Mercy, Michel Jadot, Thierry Arnould

Research output: Contribution to journalArticle

Abstract

Background information. mtDNA (mitochondrial DNA) mutations that impair oxidative phosphorylation can contribute to carcinogenesis through the increased production of reactive oxygen species and through the release of proteins involved in cell motility and invasion. On the other hand, many human cancers are associated with both the up-regulation and the increased secretion of several proteases and heparanase. In the present study, we tried to determine whether the depletion in mtDNA could modulate the expression and/or the secretion of some lysosomal hydrolases in the 143B osteosarcoma cells, as these mtDNA-depleted cells are characterized by a higher degree of invasiveness than the parental cells. Results. In comparison with the parental cells, we measured a higher amount of procathepsin B in the conditioned culture medium of the 143B cells lacking mtDNA (ρ0 143B cells), as well as a rise in the specific activity of intracellular cathepsin B. In addition, we observed an activation of the transcription factor NF-ΚB (nuclear factor ΚB) in the cells devoid of functional mitochondria. Finally, we demonstrated that the down-regulation of the NF-ΚB p65 subunit by RNA interference led to a reduction in cathepsin B expression in ρ0 143B cells. Conclusions. The up-regulation of cathepsin B by NF-ΚB, followed by its secretion into the extracellular environment, might be partly responsible for the previously reported invasiveness of the mtDNA-depleted 143B osteosarcoma cells.

Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalBiology of the Cell
Volume101
Issue number1
DOIs
Publication statusPublished - 25 Jun 2009

Keywords

  • Invasiveness
  • Lysosomal protease
  • Mitochondrial dysfunction
  • Nuclear factor κB (NF-κB)

Fingerprint Dive into the research topics of 'Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells'. Together they form a unique fingerprint.

  • Equipment

  • Cite this