TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72639
Title:
TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.
Authors:
Romeo, Salvatore; Eyden, Brian P; Prins, Frans A; Briaire-de Bruijn, Inge H; Taminiau, Antonie H M; Hogendoorn, Pancras C W
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.
Affiliation:
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Citation:
TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone. 2006, 208 (1):26-34 J. Pathol.
Journal:
The Journal of Pathology
Issue Date:
Jan-2006
URI:
http://hdl.handle.net/10541/72639
DOI:
10.1002/path.1887
PubMed ID:
16278817
Type:
Article
Language:
en
ISSN:
0022-3417
Appears in Collections:
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Full metadata record

DC FieldValue Language
dc.contributor.authorRomeo, Salvatore-
dc.contributor.authorEyden, Brian P-
dc.contributor.authorPrins, Frans A-
dc.contributor.authorBriaire-de Bruijn, Inge H-
dc.contributor.authorTaminiau, Antonie H M-
dc.contributor.authorHogendoorn, Pancras C W-
dc.date.accessioned2009-07-06T15:41:27Z-
dc.date.available2009-07-06T15:41:27Z-
dc.date.issued2006-01-
dc.identifier.citationTGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone. 2006, 208 (1):26-34 J. Pathol.en
dc.identifier.issn0022-3417-
dc.identifier.pmid16278817-
dc.identifier.doi10.1002/path.1887-
dc.identifier.urihttp://hdl.handle.net/10541/72639-
dc.description.abstractChondromyxoid 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.en
dc.language.isoenen
dc.subjectBone Canceren
dc.subjectCancer Genesen
dc.subjectCancer Proteinsen
dc.subject.meshActins-
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshBone Neoplasms-
dc.subject.meshCalcium-Binding Proteins-
dc.subject.meshCalmodulin-Binding Proteins-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshChild-
dc.subject.meshChondroblastoma-
dc.subject.meshChondrocytes-
dc.subject.meshDesmin-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshFibronectins-
dc.subject.meshGenes, Neoplasm-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMale-
dc.subject.meshMicrofilament Proteins-
dc.subject.meshMicroscopy, Electron-
dc.subject.meshMicroscopy, Immunoelectron-
dc.subject.meshMiddle Aged-
dc.subject.meshMuscle Proteins-
dc.subject.meshMuscle, Smooth-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshPlasminogen Activator Inhibitor 1-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSignal Transduction-
dc.subject.meshTransforming Growth Factor beta-
dc.subject.meshTransforming Growth Factor beta1-
dc.titleTGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.en
dc.identifier.journalThe Journal of Pathologyen
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