Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis
Issued Date
2023-01-01
Resource Type
ISSN
09147470
eISSN
17490774
Scopus ID
2-s2.0-85143266478
Pubmed ID
36456782
Journal Title
Human Cell
Volume
36
Issue
1
Start Page
456
End Page
467
Rights Holder(s)
SCOPUS
Bibliographic Citation
Human Cell Vol.36 No.1 (2023) , 456-467
Suggested Citation
Thongchot S., Duangkaew S., Yotchai W., Maungsomboon S., Phimolsarnti R., Asavamongkolkul A., Thuwajit P., Thuwajit C., Chandhanayingyong C. Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis. Human Cell Vol.36 No.1 (2023) , 456-467. 467. doi:10.1007/s13577-022-00823-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82338
Title
Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis
Author's Affiliation
Other Contributor(s)
Abstract
Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor derived from the synovium of the tendon sheath and joints, most frequently in the large joints. The standard of care for TGCTs is surgical resection. A new targeting approach for treating TGCTs has emerged from studies on the role of the CSF1/CSF1 receptor (CSF1R) in controlling cell survival and proliferation during the pathogenesis of TGCTs. We established four novel cell lines isolated from the primary tumor tissues of patients with TGCTs. The cell lines were designated Si-TGCT-1, Si-TGCT-2, Si-TGCT-3, and Si-TGCT-4, and the TGCT cells were characterized by CSF1R and CD68. These TGCT cells were then checked for cell proliferation using an MTT assay and three-dimensional spheroid. The responses to pexidartinib (PLX3397) and sotuletinib (BLZ945) were evaluated by two-dimensional MTT assays. All cells were positive for α‑smooth muscle actin (α‑SMA), fibroblast activation protein (FAP), CSF1R, and CD68. Except for Si-TGCT-4, all TGCT cells had high CSF1R expressions. The cells exhibited continuous growth as three-dimensional spheroids formed. Treatment with pexidartinib and sotuletinib inhibited TGCT cell growth and induced cell apoptosis correlated with the CSF1R level. Only Si-TGCT-4 cells demonstrated resistance to the drugs. In addition, the BAX/BCL-2 ratio increased in cells treated with pexidartinib and sotuletinib. With the four novel TGCT cell lines, we have an excellent model for further in vitro and in vivo studies.