MMP and TIMP gene expression in head and neck squamous cell carcinomas and adjacent tissues.
OBJECTIVE
To compare the frequency of gene expression of matrix metalloproteinases (MMP) stromelysins -1, -2 and -3 (MMP-3, -10, and -11), matrilysin (MMP-7), MTI-MMP (MMP-14), and of TIMPs (Tissue Inhibitors of MMPs) -1, -2, -3 and -4 in head and neck squamous cell carcinomas with those of matched adjacent normal tissues.


METHODS
The present study included 20 surgically removed head and neck squamous cell carcinomas, seven of which were accompanied by matched adjacent oral mucosa excised from the border of the specimens outside the tumor area. RNA isolated from tumors and control samples was subjected to RT-PCR using primers specific for MMP-3, -7, -10, -11 and -14 and for TIMPs -1, -2, -3, and -4.


RESULTS
Our findings demonstrate that each of the five MMP genes studied were expressed in essentially all the tumors, while the adjacent marginal tissue samples showed a more varied picture: while stromelysin-3 was located to a majority of the marginal samples, matrilysin was expressed in four of seven adjacent samples, stromelysin-1 and MTI-MMP genes were each expressed in three of these samples, and stromelysin-2 transcript was only expressed in two marginal tissue samples. Whereas TIMP-1 and TIMP-2 transcripts were identified in all tumor and adjacent tissue samples studied, TIMP-3 was expressed, albeit often at low levels, in 17 of 20 tumor samples but only in three of seven adjacent tissues. The novel TIMP-4 gene was not expressed at all.


CONCLUSIONS
Specific MMP (MMP-3, -7, -10, -14) and TIMP-3 transcripts observed in head and neck squamous cell carcinomas compared to their frequency in specimens of matching tissues provide important information about expression of extracellular matrix degrading enzymes and their tissue inhibitors in head and neck carcinomas.
Birkedal-Hansen
B
B
Matrix Extracellular Pathology Section, Laboratory of Pathology, DCS, NCI, NIH, Bethesda, MD 20892, USA. bentebh@helix.nih.gov
Pavelic
Z P
ZP
Gluckman
J L
JL
Stambrook
P
P
Li
Y Q
YQ
Stetler-Stevenson
W G
WG
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D053506:Matrix Metalloproteinase 10; D053507:Matrix Metalloproteinase 11; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D009061:Mouth Mucosa / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics; D012313:RNA / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D014158:Transcription, Genetic; D000097792:Tissue Inhibitor of Metalloproteinase-4
D004791:Enzyme Inhibitors; D006023:Glycoproteins; D053506:Matrix Metalloproteinase 10; D053507:Matrix Metalloproteinase 11; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D012313:RNA; D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4