Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern

• Published in: Experimental and molecular pathology 2005-10, Vol.79 (2), p.151-160
• Main Authors: Yucel, Taskin, Mutnal, Amar, Fay, Kevin, Fligiel, Suzanne E.G., Wang, Timothy, Johnson, Timothy, Baker, Shan R., Varani, James
• Format: Article
• Language: English
• Subjects: Basal cell carcinoma; Biological and medical sciences; Blotting, Western; Carcinoma, Basal Cell - enzymology; Carcinoma, Basal Cell - pathology; Collagen; Collagen - metabolism; Collagen - ultrastructure; Collagen fragments; Collagenase; Culture Media, Conditioned - metabolism; Dermatology; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Gelatin - metabolism; Gelatinase; Humans; Investigative techniques, diagnostic techniques (general aspects); Matrix Metalloproteinases - biosynthesis; Medical sciences; Microscopy, Electron, Transmission; Organ Culture Techniques; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptide Fragments - metabolism; Skin Neoplasms - enzymology; Skin Neoplasms - pathology; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2005.05.003

Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm.