Human and rat malignant-tumor-associated mRNAs encode stromelysin-like metalloproteinases.
Rat transin and human stromelysin 2 mRNAs, which have been associated with malignant tumors, code for potential proteins with significant sequence homology to the metalloproteinases collagenase and stromelysin. We have used an expression system that allows easy purification of these proteins after transfection of COS cells with a vector containing the corresponding cDNA. This system has allowed us to prepare transin and stromelysin 2 as active proteinases that are inhibited by inhibitors of metalloproteinases. Further analysis of these enzymes indicates that they degrade several components of the extracellular matrix including collagen types III, IV, and V and fibronectin, as well as gelatins formed from several denatured collagen types. In addition, both transin and stromelysin 2 are capable of activating procollagenase in vitro. Thus, in malignant tumors these proteinases may act, both directly and indirectly, to degrade the extracellular matrix and permit tumor invasion of neighboring tissues.
Nicholson
R
R
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France.
Murphy
G
G
Breathnach
R
R
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D006868:Hydrolysis; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003012:Microbial Collagenase / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D005353:Fibronectins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005780:Gelatin; D003094:Collagen; D004247:DNA; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase