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

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Abstract
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‐β1) 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. Copyright © 2002 John Wiley & Sons, Ltd.
Funding Information
  • Finnish Dental Society Apollonia
  • Willhelm and Else Stockman Foundation
  • Helsinki University Research Fund
  • Finnish cancer foundation
  • Biomedicum Research Foundation
  • Oulu University Hospital