Expression and regulation of collagenase-2 (MMP-8) in head and neck squamous cell carcinomas.
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.
Moilanen
M
M
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Finland.
Pirilä
E
E
Grénman
R
R
Sorsa
T
T
Salo
T
T
D015139:Blotting, Southern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020784:Matrix Metalloproteinase 8; D013755:Tetradecanoylphorbol Acetate