Expression and regulation of collagenase-2 (MMP-8) in head and neck squamous cell carcinomas

J Pathol. 2002 May;197(1):72-81. doi: 10.1002/path.1078.


MMP-8 (collagenase-2) is the most effective collagenase to initiate type I collagen degradation. Since initiation of lysis of the surrounding collagen matrix is an essential prerequisite for carcinoma cells to spread, this study investigated the expression of MMP-8 in squamous cell carcinoma (SCC) of the head and neck in vivo and in vitro. Most of the recently established head and neck carcinoma cell lines (22/25), corresponding tumour (5/7) and dermal (2/2) fibroblasts, commercial tongue carcinoma (HSC-3 and SCC-25), and transformed keratinocyte cell lines of the tongue (IHGK) and skin (HaCaT) expressed MMP-8 mRNA analysed by the PCR method. Western blotting revealed a latent 50 kD band in concentrated culture media of carcinoma cells and corresponding tumour and dermal fibroblasts. The expression of immunoreactive MMP-8 protein was reduced 30% by transforming growth factor beta-1 (TGF-beta1) at 1 ng/ml concentration and 60% at 10 ng/ml concentration, but up-regulated 2- and 2.5-fold after 10 nM and 100 nM phorbol 12-myristate 13 acetate (PMA), respectively. Immunohistological staining localized MMP-8 protein in a few malignant invading tumour cell islands, certain fibroblasts, polymorphonuclear neutrophils (PMNs), and plasma cells. In situ hybridization revealed a faint sporadic signal in carcinoma cells of all eight tissue sections analysed. It is concluded that tissue from head and neck carcinomas can express MMP-8 both in vivo and in vitro. Since the amount of MMP-8 in carcinoma and stromal cells is rather low, MMP-8 may have a potential role, with other collagenases, in the proteolysis of connective tissue associated with the spreading of invasive carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / genetics
  • Humans
  • In Situ Hybridization
  • Male
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 8 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured


  • RNA, Messenger
  • RNA, Neoplasm
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 8
  • Tetradecanoylphorbol Acetate