Transin/stromelysin expression in rheumatoid synovium. A transformation-associated metalloproteinase secreted by phenotypically invasive synoviocytes.
Transin is a neutral metalloproteinase whose mRNA was first isolated from rat fibroblasts that had undergone malignant transformation. The protein is highly expressed in malignant rather than benign animal tumors. Its human analog is stromelysin, a 51-kd metalloproteinase initially isolated from cultured human synoviocytes. Northern blot analysis demonstrated that rheumatoid arthritis synovial tissue contained significantly higher levels of stromelysin mRNA than did osteoarthritis synovial tissue. Cultured synoviocytes were also shown to express stromelysin mRNA, and an affinity-purified anti-peptide antiserum to stromelysin specifically immunoprecipitated the stromelysin protein from the conditioned medium of cultured explant rheumatoid synoviocytes. Immunohistochemical staining of rheumatoid synovium demonstrated specific cytoplasmic staining of cells of the synovial lining layer, stromal fibroblasts, and endothelial cells. Osteoarthritic synovia showed significantly less stromelysin staining. Similarly, rheumatoid synovia demonstrated marked nuclear staining for the proliferation- and transformation-associated Myc oncoprotein. In contrast, osteoarthritic synovia showed negligible staining. These results support the belief that the proliferative, invasive behavior of rheumatoid synoviocytes reflects the expression of biochemical features generally associated with phenotypically transformed, malignant tumors. Clearly not a malignancy, the rheumatoid synovium appears to be paracrine driven by mediators generated in local inflammatory milieu.
Case
J P
JP
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892.
Lafyatis
R
R
Remmers
E F
EF
Kumkumian
G K
GK
Wilder
R L
RL
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D010641:Phenotype; D011506:Proteins / Q000378:metabolism; D011519:Proto-Oncogenes / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3