title: TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.
abstract: Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architecture containing stellate and myofibroblast-like spindle cells. The aim of this study was to investigate the presence, spatial distribution, and extent of myoid differentiation in CMF and to evaluate a possible causative role for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA) expression. Twenty cases were studied for immunoreactivity for muscle-specific actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation was further investigated ultrastructurally, including immuno-electron microscopy using antibodies against MSA and SMA, focusing upon the different cell types in CMF. The expression of potential genes driving this process was quantified by Q-RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells, especially those with a spindled morphology, showed diffuse immunoreactivity for MSA, SMA, TGF-beta1, and PAI-1, while desmin, h-caldesmon, and calponin were absent. Ultrastructurally, neoplastic cells showed the presence of myofilaments and rare dense bodies, which were more prominent in spindle cells and less so in chondroblast-like cells. Immuno-electron microscopy confirmed the actin nature of these myofilaments. No fibronexus was identified. The functional activity of TGF-beta1 was demonstrated by the identification of PAI-1, a related downstream molecule both immunohistochemically as well as by Q-RT-PCR. There was a linear correlation between TGF-beta1 and PAI-1 expression. Fibronectin-EDA levels were low. We have therefore substantiated the presence of morphological, immunohistochemical, and immuno-electron microscopic partial myofibroblastic differentiation in CMF, driven by TGF-beta1 signalling.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Romeo
authors.forename: Brian
authors.initials: B
authors.lastname: Eyden
authors.forename: Frans A
authors.initials: FA
authors.lastname: Prins
authors.forename: Inge H
authors.initials: IH
authors.lastname: Briaire-de Bruijn
authors.forename: Antonie H M
authors.initials: AH
authors.lastname: Taminiau
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D000199:Actins / Q000276:immunology; D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000276:immunology; D002148:Calmodulin-Binding Proteins / Q000276:immunology; D002471:Cell Transformation, Neoplastic; D002648:Child; D002804:Chondroblastoma / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D019902:Chondrocytes / Q000473:pathology / Q000648:ultrastructure; D003893:Desmin / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008840:Microfilament Proteins; D008854:Microscopy, Electron / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D009124:Muscle Proteins / Q000276:immunology; D009130:Muscle, Smooth / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D003893:Desmin; D005353:Fibronectins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000096985:Calponins; C508960:TGFB1 protein, human