Abstract
We previously demonstrated that overexpression of cathepsin B (CB) protease in oral squamous cell carcinomas correlated positively with advanced tumor stage and poor histologic malignancy grade. Here we examined whether CB contributes to the invasiveness of oral carcinoma cells. For RNA-mediated inhibition, two ribozymes that target CB mRNA were designed and stably expressed in the oral squamous cell carcinoma cell line 1386Tu. Both ribozymes diminished expression of CB mRNA, protein, and activity, without affecting cathepsin D or β-actin, as determined by quantitative real-time PCR, Western blots, and protease activity assays. Matrigel invasion assays showed that the invasiveness of the cells was significantly reduced by the expressed ribozymes and, surprisingly, the motilities of the ribozyme-transfected cells were also diminished. Our results document a direct role for CB in promoting oral cancer spread and invasion, and open the possibility of controlling oral carcinoma malignancy and metastasis by targeting CB with RNA inhibitor strategies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 187-195 |
| Number of pages | 9 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 436 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 1 2005 |
| Externally published | Yes |
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Keywords
- Cathepsin
- Gene therapy
- Invasion
- Motility
- Oral carcinoma
- Ribozyme
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Cathepsin B promotes both motility and invasiveness of oral carcinoma cells. / Wickramasinghe, Nalinie S.; Nagathihalli, Nagaraj; Vigneswaran, Nadarajah; Zacharias, Wolfgang.
In: Archives of Biochemistry and Biophysics, Vol. 436, No. 1, 01.04.2005, p. 187-195.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cathepsin B promotes both motility and invasiveness of oral carcinoma cells
AU - Wickramasinghe, Nalinie S.
AU - Nagathihalli, Nagaraj
AU - Vigneswaran, Nadarajah
AU - Zacharias, Wolfgang
PY - 2005/4/1
Y1 - 2005/4/1
N2 - We previously demonstrated that overexpression of cathepsin B (CB) protease in oral squamous cell carcinomas correlated positively with advanced tumor stage and poor histologic malignancy grade. Here we examined whether CB contributes to the invasiveness of oral carcinoma cells. For RNA-mediated inhibition, two ribozymes that target CB mRNA were designed and stably expressed in the oral squamous cell carcinoma cell line 1386Tu. Both ribozymes diminished expression of CB mRNA, protein, and activity, without affecting cathepsin D or β-actin, as determined by quantitative real-time PCR, Western blots, and protease activity assays. Matrigel invasion assays showed that the invasiveness of the cells was significantly reduced by the expressed ribozymes and, surprisingly, the motilities of the ribozyme-transfected cells were also diminished. Our results document a direct role for CB in promoting oral cancer spread and invasion, and open the possibility of controlling oral carcinoma malignancy and metastasis by targeting CB with RNA inhibitor strategies.
AB - We previously demonstrated that overexpression of cathepsin B (CB) protease in oral squamous cell carcinomas correlated positively with advanced tumor stage and poor histologic malignancy grade. Here we examined whether CB contributes to the invasiveness of oral carcinoma cells. For RNA-mediated inhibition, two ribozymes that target CB mRNA were designed and stably expressed in the oral squamous cell carcinoma cell line 1386Tu. Both ribozymes diminished expression of CB mRNA, protein, and activity, without affecting cathepsin D or β-actin, as determined by quantitative real-time PCR, Western blots, and protease activity assays. Matrigel invasion assays showed that the invasiveness of the cells was significantly reduced by the expressed ribozymes and, surprisingly, the motilities of the ribozyme-transfected cells were also diminished. Our results document a direct role for CB in promoting oral cancer spread and invasion, and open the possibility of controlling oral carcinoma malignancy and metastasis by targeting CB with RNA inhibitor strategies.
KW - Cathepsin
KW - Gene therapy
KW - Invasion
KW - Motility
KW - Oral carcinoma
KW - Ribozyme
UR - http://www.scopus.com/inward/record.url?scp=14744302879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14744302879&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2005.01.023
DO - 10.1016/j.abb.2005.01.023
M3 - Article
C2 - 15752724
AN - SCOPUS:14744302879
VL - 436
SP - 187
EP - 195
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 1
ER -