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

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

doi:10.1002/(sici)1097-0215(19991112)83:4<526::aid-ijc15>3.0.co;2-m

Cited by 83 publications

(39 citation statements)

References 18 publications

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“…The ability of cystatin M to inhibit migration and invasion of MDA-MB-435S cells through Matrigel was consistent with previous reports on the inhibition of migration and invasion by stefin A (cystatin A), cystatin C, and E-64 (Boike et al, 1992;Kobayashi et al, 1992;Redwood et al, 1992;Sexton and Cox, 1997;Kolkhorst et al, 1998;Coulibaly et al, 1999;Konduri et al, 2002). However, the extent of inhibition of invasion by cystatin M observed in the present study, that is, X95%, suggested that cystatin M may target some cysteine protease(s) that was rate-limiting in the proteolytic cascade, leading to matrix dissolution and invasion.…”

Section: Discussionsupporting

confidence: 93%

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells

et al. 2003

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Proteases are involved in many aspects of tumor progression, including cell survival and proliferation, escape from immune surveillance, cell adhesion and migration, remodeling and invasion of the extracellular matrix. Several lysosomal cysteine proteases have been cloned and shown to be overexpressed in cancer; yet, despite the great potential for development of novel therapeutics, we still know little about the regulation of their proteolytic activity. Cystatins such as cystatin M are potent endogenous protein inhibitors of lysosomal cysteine proteases. Cystatin M is expressed in normal and premalignant human epithelial cells, but not in many cancer cell lines. Here, we examined the effects of cystatin M expression on malignant properties of human breast carcinoma MDA-MB-435S cells. Cystatin M was found to significantly reduce in vitro: cell proliferation, migration, Matrigel invasion, and adhesion to endothelial cells. Reduction of cell proliferation and adhesion to an endothelial cell monolayer were both independent of the inhibition of lysosomal cysteine proteases. In contrast, cell migration and matrix invasion seemed to rely on lysosomal cysteine proteases, as both recombinant cystatin M and E64 were able to block these processes. This study provides the first evidence that cystatin M may play important roles in safeguarding against human breast cancer.

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Section: Discussionsupporting

confidence: 93%

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells

et al. 2003

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“…The ®ndings obtained in the in vitro invasion assays are in accordance with the results obtained by the selective cysteine protease inhibitors in murine squamous carcinoma cells (Coulibaly et al, 1999) and glioblastoma cells (Demchik et al, 1999), demonstrating that cathepsin B can mediate the degradation of ECM components. Kolkhorst et al (1998) found that invasiveness of tumor cell lines expressing high levels of cathepsin B are e ciently inhibited by CA074, a selective cathepsin B inhibitor.…”

Section: Discussionsupporting

confidence: 82%

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells

et al. 2001

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Increases in abundance of cathepsin B transcript and protein correlate with increases in tumor grade and alterations in subcellular localization and activity of cathepsin B. The enzyme is able to degrade the components of the extracellular matrix (ECM) and activate other proteases capable of degrading ECM. To investigate the role played by this protease in the invasion of brain tumor cells, we transfected SNB19 human glioblastoma cells with a plasmid containing cathepsin B cDNA in antisense orientation. Control cells were transfected with vector alone. Clones expressing antisense cathepsin B cDNA exhibited signi®cant reductions in cathepsin B mRNA, enzyme activity and protein compared to controls. Matrigel Invasion assay showed that the antisense-transfected cells had a markedly diminished invasiveness compared with controls. When tumor spheroids containing antisense transfected SNB19 cells expressing reduced cathepsin B were co-cultured with fetal rat brain aggregates, invasion of fetal rat brain aggregates was signi®cantly reduced. Green Fluorescent Protein (GFP) expressing parental cells and antisense transfectants were generated for detection in mouse brain tissue without any postchemical treatment. Intracerebral injection of SNB19 stable antisense transfectants resulted in reduced tumor formation in nude mice. These results strongly support a role for cathepsin B in the invasiveness of human glioblastoma cells and suggest cathepsin B antisense may prove useful in cancer therapy. Oncogene (2001) 20, 3665 ± 3673.

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“…Recent studies using molecular genetic techniques to manipulate cathepsin B levels in established tumor cell lines have shown conflicting results for the contributions of cysteine proteinase B to cell motility. The motility of murine squamous carcinoma cells was unaffected by stable transfection of human cathepsin B cDNA, in spite of a threefold increase in the level of secreted pro-cathepsin B (Coulibaly et al, 1999). Decreasing cathepsin B activity by cathepsin B antisense expression plasmid was found to have no effect on the motility of human melanoma (A375M) and prostate carcinoma (PC3M) cells (Szpaderska and Frankfater, 2001).…”

Section: Discussionmentioning

confidence: 99%

Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis

et al. 2004

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The cysteine proteinase cathepsin B has been implicated in tumor progression by virtue of its increased mRNA and protein levels, as well as its localization at the invading front of the tumor. In this study, we examined whether blocking cathepsin B expression in human glioblastoma SNB19 cells affects angiogenesis. Stable transfectants of human glioblastoma cells with a plasmid containing antisense cathepsin B cDNA showed decreased migration rates in wound-and spheroid-migration assays. Analysis showed a reduction in VEGF protein and MMP-9 activity in the cathepsin B antisense cDNA-transfected cells. Regarding angiogenesis in vitro, we found that the conditioned medium of glioblastoma cells with downregulated cathepsin B expression reduced cell-cell interaction of human microvascular endothelial cells, resulting in the disruption of capillary-like network formation. Furthermore, a marked reduction in microvasculature development was seen in an in vivo dorsal air sac assay of glioblastoma cells with downregulated cathepsin B expression. Taken together, these results provide evidence that inhibition of cathepsin B expression can suppress glioblastoma-induced neovascularization.

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

Cited by 83 publications

References 18 publications

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells

Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis

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