EXPRESSION OF TYPE-IV COLLAGEN AND ITS DEGRADING ENZYMES IN SQUAMOUS-CELL CARCINOMA OF LUNG

We examined the in situ distribution of basement membrane collagen (Col IV), matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) by immunohistochemistry and their mRNA levels by Northern blot analysis in 14 cases of squamous cell carcinoma of the lung. Elevated mRNA levels of MMP-2 and Col IV were demonstrated in all the cases examined and were associated with in situ disruption of basement membranes around the tumor nests. In contrast, TIMP-1 mRNA levels were not altered. MMP-2, MMP-9 and TIMP-1 were localized in tumor cells, stromal fibroblasts and endothelial cells. There were no significant correlations between these parameters and clinical staging. The results suggest that the degrading enzymes of basement membrane collagen play an important role in the invasion and metastasis of human squamous cell carcinoma of the lung.