Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF-1, driving tenosynovial giant cell tumor Journal Article


Authors: Chandler, A. C.; Yakoub, M.; Fujiwara, T.; Donlin, L. T.; Purdue, P. E.; Healey, J. H.
Article Title: Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF-1, driving tenosynovial giant cell tumor
Abstract: Tenosynovial giant cell tumor (TCGT) is a rare neoplasm affecting the synovium of joints, bursae, and tendon sheaths. The overproduction of colony-stimulating factor-1 (CSF-1) by a minority of the tumor population works in a paracrine fashion to drive tumor growth. Pathology of the reactive, monocytic component has been well elucidated, whereas the populations of neoplastic cells and all the sources of CSF-1 overproduction are incompletely characterized. Podoplanin (PDPN), or gp38, is a cell surface glycoprotein that is expressed on fibroblast-like synovial cells and upregulated in rheumatoid arthritis and many cancers; it governs cell mobility, epithelial–mesenchymal transition, and other functions and is associated with lymphangiogenesis and poor prognosis in many solid tumors, which underscores its local and possible systemic effects. We found higher PDPN expression in TGCT than in internal controls of patients' healthy synovium. Flow cytometry partitioned PDPNhigh cells into PDPNhighCD90+ and PDPNhighCD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhighCD90+ cells revealed that CSF-1 expression was 10-fold higher than in PDPNhighCD14+ cells. Therefore, we conclude that the lining fibroblast-like synovial cells, which express PDPNhighCD90+, are responsible for the overproduction of CSF-1 and for driving tumor growth. © 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.
Keywords: clinical article; controlled study; human tissue; protein expression; human cell; flow cytometry; metabolism; gene expression; transcription factor; pathology; cell population; transcription factors; podoplanin; immunocytochemistry; tumor cell; fibroblast; cytokine production; rheumatoid arthritis; real time polymerase chain reaction; monocyte; fluorescence activated cell sorting; antibody; cd14 antigen; colony stimulating factor 1; desmin; antibody conjugate; synovial membrane; synoviocyte; synovium; arthritis, rheumatoid; tenosynovial giant cell tumor; dilution; macrophage colony-stimulating factor; humans; human; article; cd14; giant cell tumor of tendon sheath; thy 1 membrane glycoprotein; cd90; csf-1; synoviocytes; thy-1 antigens
Journal Title: Journal of Orthopaedic Research
Volume: 40
Issue: 8
ISSN: 0736-0266
Publisher: John Wiley & Sons  
Date Published: 2022-08-01
Start Page: 1918
End Page: 1925
Language: English
DOI: 10.1002/jor.25216
PUBMED: 34855235
PROVIDER: scopus
PMCID: PMC9160208
DOI/URL:
Notes: Article -- Export Date: 2 September 2022 -- Source: Scopus
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  1. John H Healey
    548 Healey
  2. Mohamed Ahmed Ali Yakoub
    17 Yakoub