Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern.
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.
Yucel
Taskin
T
Department of Otolaryngology-Head and Neck Surgery, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Mutnal
Amar
A
Fay
Kevin
K
Fligiel
Suzanne E G
SE
Wang
Timothy
T
Johnson
Timothy
T
Baker
Shan R
SR
Varani
James
J
D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000201:enzymology* / Q000473:pathology; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D046529:Microscopy, Electron, Transmission; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000378:metabolism*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology
D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D005780:Gelatin; D003094:Collagen; D020782:Matrix Metalloproteinases