Cathepsin B promotes both motility and invasiveness of oral carcinoma cells

Nalinie S. Wickramasinghe, Nagathihalli S. Nagaraj, Nadarajah Vigneswaran, Wolfgang Zacharias

Research output: Contribution to journalArticle

28 Scopus citations

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 languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume436
Issue number1
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Keywords

  • Cathepsin
  • Gene therapy
  • Invasion
  • Motility
  • Oral carcinoma
  • Ribozyme

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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