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

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

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 122 KB
• Volume: 83
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19991112)83:4<526::aid-ijc15>3.0.co;2-m

✦ Synopsis

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.