Targeted inhibition of human collagenase-3 (MMP-13) expression inhibits squamous cell carcinoma growth in vivo

Oncogene. 2004 Jul 1;23(30):5111-23. doi: 10.1038/sj.onc.1207678.


Squamous cell carcinomas (SCCs) of the head and neck are characterized by a high tendency for local invasion and metastasis to lymph nodes. Collagenase-3 (MMP-13) is specifically expressed by tumor cells in SCCs of the head and neck and its expression correlates with their invasion capacity. To specifically examine the role of MMP-13 in the growth and invasion of SCC, we constructed a hammerhead ribozyme targeted against human MMP-13 mRNA. The anti-MMP-13 ribozyme effectively cleaved MMP-13 transcripts in vitro. Adenoviral delivery of the anti-MMP-13 ribozyme to cutaneous metastatic SCC cells in culture resulted in potent and specific inhibition of the production of proMMP-13 and markedly suppressed invasion of SCC cells through Matrigel. In addition, adenoviral delivery of anti-MMP-13 ribozyme promoted apoptosis in SCC cells within 72 h. Intratumoral injection of anti-MMP-13 ribozyme coding adenovirus into human SCC xenografts established in SCID mice potently suppressed tumor growth, inhibited MMP-13 expression and gelatinolytic activity and reduced the number of proliferating cells within the tumors. These results provide evidence for an important role for MMP-13 in SCC growth and invasion and identify MMP-13 as a promising target for ribozyme-based therapy of SCC in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology
  • Cell Division
  • Cell Survival
  • Collagen / metabolism
  • Collagen / pharmacology
  • Collagenases / genetics
  • Collagenases / metabolism
  • Drug Combinations
  • Gelatinases / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Keratinocytes / cytology
  • Keratinocytes / enzymology
  • Laminin
  • Male
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Proteoglycans
  • RNA, Messenger / genetics
  • Time Factors
  • Tumor Cells, Cultured


  • Drug Combinations
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • Proteoglycans
  • RNA, Messenger
  • matrigel
  • Collagen
  • Collagenases
  • Gelatinases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse