Expression of MMP-7, MMP-9, TIMP-1 and TIMP-2 mRNA in lung tissue of patients with non-small cell lung cancer (NSCLC) and benign pulmonary disease.
The expression of matrix metallo-proteinases (MMP-7 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), which are involved in the degradation of the extracellular matrix (ECM) and tumor growth, was investigated in normal lung tissue, tissue of benign pulmonary diseases and non-small cell lung cancer (NSCLC) tissue.


METHODS
Tumor tissue and surrounding carcinoma-free lung tissue samples were obtained from 91 patients with NSCLC who had undergone surgery in the years 2005-2007 as well as lung tissue from 12 patients operated on for 'benign' bullous emphysema or interstitial lung disease. The mRNA was isolated from the tissues and the expression of mRNA was assessed using a real-time RT PCR method.


RESULTS
Significantly higher expression of MMP-7, MMP-9 and TIMP-1 mRNA was demonstrated in the NSCLC tissue in comparison with the normal lung tissue from the same patients (p=0.0003, p<0.0001 and p=0.0018, respectively). Similar results for MMP-7, MMP-9 and TIMP-1 were found in the histological subgroups: squamous cell lung cancer vs. normal tissue (p=0.0198, p=0.0015 and p=0.0366, respectively), and adenocarcinoma vs. normal tissue (p=0.0045, p<0.0001 and p=0.0140, respectively). The expression of MMP-7 was found to be significantly higher in tumor tissue vs. lung tissue of the benign diseases (p=0.0086) and similar results were also recorded in the histological subgroups: squamous cell lung cancer vs. benign tissue (p=0.0171) and adenocarcinoma vs. benign tissue (p=0.0135). The expression of MMP-9 was significantly higher only in the adenocarcinoma subgroup vs. the benign tissue (p=0.0412). No differences in the expression of mRNA between stage IA and stages IB-IIIB of NSCLC were recorded.


CONCLUSIONS
Significantly higher expression of MMP-7 and MMP-9 in tumor tissue than in the surrounding tissue or in benign lung disease tissue supports the notion of an important role of these metalloproteinases in the growth of lung carcinoma. TIMP-1 expression is increased only in carcinoma, but not in benign lung disease.
Safranek
J
J
Departments of Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, University Hospital in Pilsen, Czech Republic.
Pesta
M
M
Holubec
L
L
Kulda
V
V
Dreslerova
J
J
Vrzalova
J
J
Topolcan
O
O
Pesek
M
M
Finek
J
J
Treska
V
V
D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008171:Lung Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9