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 PDPNhigh CD90+ and PDPNhigh CD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhigh CD90+ cells revealed that CSF-1 expression was 10-fold higher than in PDPNhigh CD14+ cells. Therefore, we conclude that the lining fibroblast-like synovial cells, which express PDPNhigh CD90+ , are responsible for the overproduction of CSF-1 and for driving tumor growth.

• Authors: Andrew C Chandler, Mohamed Yakoub, Tomohiro Fujiwara, Laura T Donlin, Paul Edward Purdue, John H Healey
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 40 Issue 8 Pg. 1918-1925 (08 2022) ISSN: 1554-527X [Electronic] United States
• PMID: 34855235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.

Chemical References

• Thy-1 Antigens
• Transcription Factors
• Macrophage Colony-Stimulating Factor

Topics

• Arthritis, Rheumatoid (metabolism)
• Giant Cell Tumor of Tendon Sheath (metabolism, pathology)
• Humans
• Macrophage Colony-Stimulating Factor (metabolism)
• Neoplasms
• Synovial Membrane
• Synoviocytes (metabolism)
• Thy-1 Antigens
• Transcription Factors (metabolism)