Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas.
BACKGROUND
Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC).


METHODS
Of 48 laryngeal squamous cell carcinoma (LSCC) biopsies and 10 HNSCC cell lines, mRNA was isolated, reversely transcribed, and subjected to polymerase chain reaction (PCR) amplifying MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, and TIMP-2. Silver nitrate-stained gel electrophoresis demonstrated MMP and TIMP expression status. Exemplary immunohistochemistry and zymography confirmed translation and enzyme activity.


RESULTS
Densitometric analysis revealed MMP-2 expression and lymph node metastases to be positively and TIMP-1 and TIMP-2 to be negatively correlated with lymph node metastases. TIMP-2 expression and tumor size were negatively correlated. MMP-1, MMP-9, and MMP-10 expression were not correlated to metastasis formation or tumor size.


CONCLUSIONS
Our results suggest that MMP-2 expression enhances, whereas TIMP-1 and TIMP-2 both suppress, cancer spread in LSCC.
Görögh
Tibor
T
Department of Otorhinolaryngology, Head and Neck Surgery, University of Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 14, 24105 Kiel, Germany. gorogh@hno.uni-kiel.de
Beier
Ulf H
UH
Bäumken
Jens
J
Meyer
Jens E
JE
Hoffmann
Markus
M
Gottschlich
Stefan
S
Maune
Steffen
S
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D017421:Sequence Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases