TY - JOUR
T1 - Cathepsin B promotes both motility and invasiveness of oral carcinoma cells
AU - Wickramasinghe, Nalinie S.
AU - Nagaraj, Nagathihalli S.
AU - Vigneswaran, Nadarajah
AU - Zacharias, Wolfgang
N1 - Funding Information:
This work was supported by NIH Grant DE13150 and by Philip Morris USA and Philip Morris International, and by a postdoctoral fellowship award from the University of Louisville Brown Cancer Center. We thank Peter Sacks (Division of Biological Sciences, College of Dentistry, New York University, New York), for the generous gift of his cell line MDA-1386Tu.
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
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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 -
