Upregulation of matrix metalloproteinase-1 (MMP-1) expression in oral carcinomas of betel quid (BQ) users: roles of BQ ingredients in the acceleration of tumour cell motility through MMP-1

Arch Oral Biol. 2008 Sep;53(9):810-8. doi: 10.1016/j.archoralbio.2008.05.004. Epub 2008 Jun 20.


Matrix metalloproteinases (MMPs) are commonly expressed in carcinomas including oral squamous cell carcinomas (OSCCs). On the other hand, some evidences suggested that ingredients of betel quid (BQ) inhibit the activity and/or expression of some MMPs thought to be the pathogenesis of oral submucous fibrosis. This study was to analyse whether MMP-1 expression is inhibited in OSCC specimens from BQ users and in cell lines survived from the challenge of BQ ingredients. We found that MMP-1 mRNA was expressed in all the tested 27 OSCC. Levels of MMP-1 mRNA and protein were significantly elevated in the tested five OSCC specimens than in their adjacent tissues (P<0.001 and 0.05, respectively). Esophageal carcinoma (CE81T/VGH) and OSCC (OECM-1) cell lines survived from the cytotoxic BQ extract (BQE) and arecoline selection process were found to express higher MMP-1 mRNA and protein levels, or to exhibit a significant acceleration of two-dimensional (2D) motility than their non-selected parental cells. The enhanced motility was further demonstrated to be specifically and significantly inhibited by the MMP-1 neutralizing antibody and/or by the transfection of an MMP-1 specific antisense oligodeoxynucleotide. These results suggest that in some carcinomas of the upper aerodigestive tract, BQ usage may upregulate MMP-1 expression in the survived tumour cells, and increase their mobility in an MMP-1-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Areca / adverse effects*
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Movement / drug effects
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 8 / metabolism
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / metabolism*
  • Oral Submucous Fibrosis / chemically induced
  • Oral Submucous Fibrosis / metabolism*
  • Plant Structures / adverse effects*
  • Plant Structures / metabolism
  • Precancerous Conditions / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects


  • RNA, Messenger
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 1