Modulation of invasive properties of murine squamous carcinoma cells by heterologous expression of cathepsin B and cystatin C
Författare
Summary, in English
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.
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.
Avdelning/ar
Publiceringsår
1999
Språk
Engelska
Sidor
526-531
Publikation/Tidskrift/Serie
International Journal of Cancer
Volym
83
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Cancer and Oncology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0020-7136