Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro

BMC Cancer. 2008 Jun 30:8:182. doi: 10.1186/1471-2407-8-182.

Abstract

Background: Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas.

Methods: Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels.

Results: Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma.

Conclusion: These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblastoma / enzymology*
  • Ameloblastoma / genetics
  • Ameloblastoma / pathology
  • Humans
  • Jaw Neoplasms / enzymology*
  • Jaw Neoplasms / genetics
  • Jaw Neoplasms / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Neoplasm Invasiveness
  • Plasmids / genetics
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Matrix Metalloproteinase Inhibitors
  • RNA, Messenger
  • RNA, Small Interfering
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2