巨细胞
细胞瘤
巨细胞瘤
生物
癌症研究
肿瘤转化
细胞
骨巨细胞瘤
旁观者效应
自分泌信号
病理
癌症
受体
癌变
医学
免疫学
遗传学
作者
David G.P. van IJzendoorn,Magdalena Matusiak,Gregory W. Charville,Geert Spierenburg,Sushama Varma,Deana Colburg,Michiel A. J. van de Sande,Kirsten van Langevelde,David G. Mohler,Kristen N. Ganjoo,Nam Bui,Raffi S. Avedian,Judith V.M.G. Bovée,Robert J. Steffner,Robert West,Matt van de Rijn
标识
DOI:10.1158/1078-0432.ccr-22-1898
摘要
Abstract Purpose: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. Experimental Design: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. Results: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. Conclusions: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.
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