Cathepsin B promotes both motility and invasiveness of oral carcinoma cells.
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.
Wickramasinghe
Nalinie S
NS
Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Nagaraj
Nagathihalli S
NS
Vigneswaran
Nadarajah
N
Zacharias
Wolfgang
W
D001483:Base Sequence; D015415:Biomarkers; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002401:Cathepsin B / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000378:metabolism; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016337:RNA, Catalytic / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D016337:RNA, Catalytic; D012333:RNA, Messenger; D010447:Peptide Hydrolases; D002401:Cathepsin B