Modulation of invasive properties of murine squamous carcinoma cells by heterologous expression of cathepsin B and cystatin C

Sogué Coulibaly, Herwig Schwihla, Magnus Abrahamson, Adriana Albini, Christa Cerni, Jason L. Clark, Ken M. Ng, Nobuhiko Katunuma, Otto Schlappack, Josef Glössl, Lukas Mach

Research output: Contribution to journalArticle

Abstract

Murine SCC-VII squamous carcinoma cells have the capacity to penetrate reconstituted basement membranes (Matrigel) in vitro. The invasion of Matrigel layers by SCC-VII cells was significantly reduced by E-64, a specific inhibitor of lysosomal cysteine proteinases. The cathepsin-B- selective E-64 derivative, CA-074, inhibited penetration of Matrigel by SCC- VII cells to the same extent, indicating a major role for this particular lysosomal enzyme in extracellular-matrix degradation during squamous- carcinoma-cell invasion. SCC-VII cells were stably transfected with a cDNA encoding human procathepsin B, in an attempt to modulate the invasive properties of the cell line. The transfected cells expressed the heterologous gene, secreted increased amounts of procathepsin B and displayed enhanced invasive potential. In vivo, the activity of cathepsin B is strictly regulated by endogenous inhibitors. SCC-VII cells were therefore also stably transfected with a cDNA encoding human cystatin C, the most potent cysteine- proteinase inhibitor in mammalian tissues. The expression of this transgene resulted in the production of active recombinant cystatin C and a pronounced reduction in Matrigel invasion. These studies demonstrate that the invasive properties of squamous-cell carcinomas can be changed by modulation of the balance between cathepsin B and its endogenous inhibitors, and provide further evidence for the involvement of this lysosomal cysteine proteinase in tumour invasion and metastasis.

Original languageEnglish
Pages (from-to)526-531
Number of pages6
JournalInternational Journal of Cancer
Volume83
Issue number4
DOIs
Publication statusPublished - 1999

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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