title: Plasminogen activators and their inhibitor gene expression in cutaneous NF1-related neurofibromas.
abstract: Cutaneous neurofibromatosis 1 (NF1)-related neurofibromas are benign tumors and composed of Schwann cells, perineurial cells and/or fibroblasts, endothelial cells, mast cells and macrophages. Extracellular proteolysis namely plasminogen activation (PA) operates in many tissue destructive processes. We wanted to study plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor PAI-1, which have not earlier been studied comprehensively in cutaneous NF1-related tumors. We analyzed the distribution of uPA, tPA and PAI-1 antigen level by immunohistochemistry and mRNA level by in situ hybridization, to identify which cells are primarily involved in proteolytic activity and plasminogen activation. Twelve NF1 skin tumor samples from six patients were obtained during the operations. Mast cells, macrophages and endothelial cells were distributed only locally. Their expression levels of PA components were not so notable. Large extent of tumor cells of Schwann cell origin and prominent expression levels of uPA, tPA and PAI-1 indicated that these cells are responsible for the main source of PA components in cutaneous NF1-related neurofibromas.
authors.affiliation: Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland. vappu.siren@helsinki.fi
authors.forename: Vappu
authors.initials: V
authors.lastname: Sirén
authors.forename: Juha
authors.initials: J
authors.lastname: Peltonen
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
mesh_terms: D000328:Adult; D004727:Endothelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics; D010960:Plasminogen Activators / Q000032:analysis / Q000235:genetics*; D015849:Plasminogen Inactivators / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator