PMID- 15752724 OWN - NLM STAT- MEDLINE DCOM- 20050517 LR - 20210524 IS - 0003-9861 (Print) IS - 0003-9861 (Linking) VI - 436 IP - 1 DP - 2005 Apr 1 TI - Cathepsin B promotes both motility and invasiveness of oral carcinoma cells. PG - 187-95 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 beta-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. FAU - Wickramasinghe, Nalinie S AU - Wickramasinghe NS AD - Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. FAU - Nagaraj, Nagathihalli S AU - Nagaraj NS FAU - Vigneswaran, Nadarajah AU - Vigneswaran N FAU - Zacharias, Wolfgang AU - Zacharias W LA - eng GR - R01 DE013150/DE/NIDCR NIH HHS/United States GR - DE13150/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Biomarkers) RN - 0 (Proliferating Cell Nuclear Antigen) RN - 0 (RNA, Catalytic) RN - 0 (RNA, Messenger) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.22.1 (Cathepsin B) SB - IM MH - Base Sequence MH - Biomarkers MH - Blotting, Western MH - Carcinoma, Squamous Cell/*pathology MH - Cathepsin B/*physiology MH - Cell Movement/*physiology MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - Molecular Sequence Data MH - Mouth Neoplasms/*pathology MH - Neoplasm Invasiveness MH - Neoplasm Staging MH - Peptide Hydrolases/metabolism MH - Prognosis MH - Proliferating Cell Nuclear Antigen/analysis MH - RNA, Catalytic/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Transfection MH - Tumor Cells, Cultured EDAT- 2005/03/09 09:00 MHDA- 2005/05/18 09:00 CRDT- 2005/03/09 09:00 PHST- 2005/01/06 00:00 [received] PHST- 2005/01/27 00:00 [revised] PHST- 2005/03/09 09:00 [pubmed] PHST- 2005/05/18 09:00 [medline] PHST- 2005/03/09 09:00 [entrez] AID - S0003-9861(05)00053-6 [pii] AID - 10.1016/j.abb.2005.01.023 [doi] PST - ppublish SO - Arch Biochem Biophys. 2005 Apr 1;436(1):187-95. doi: 10.1016/j.abb.2005.01.023.