Dysregulation of Zinc Finger Protein 395 Contributes to the Pathogenesis of Chondrosarcoma

Chen, Changbao; Zhou, Hua; Liu, Zhongjun; Ma, Xiaofang

doi:10.2147/ott.s310164

Cited by 2 publications

(2 citation statements)

References 32 publications

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“… 5 , 6 PBF is a DNA‐binding transcription factor that is overexpressed in human cancers, including glioblastoma, kidney cancer, osteosarcoma, Ewing sarcoma, and neuroblastoma, and plays an oncogenic role in carcinogenesis. 7 We previously reported that PBF protein is highly expressed in 92% of osteosarcoma biopsy specimens. Furthermore, patients with PBF‐positive osteosarcoma had a significantly worse prognosis than those with negative PBF expression.…”

Section: Introductionmentioning

confidence: 95%

“…We previously identified papillomavirus binding factor (PBF) as an osteosarcoma antigen recognized by an autologous cytotoxic T lymphocyte (CTL) clone 5,6 . PBF is a DNA‐binding transcription factor that is overexpressed in human cancers, including glioblastoma, kidney cancer, osteosarcoma, Ewing sarcoma, and neuroblastoma, and plays an oncogenic role in carcinogenesis 7 . We previously reported that PBF protein is highly expressed in 92% of osteosarcoma biopsy specimens.…”

Section: Introductionmentioning

confidence: 99%

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Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor

Hamada,

Tsukahara,

Watanabe

et al. 2023

Cancer Science

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We previously identified papillomavirus binding factor (PBF) as an osteosarcoma antigen recognized by an autologous cytotoxic T lymphocyte clone. Vaccination with PBF‐derived peptide presented by HLA‐A24 (PBF peptide) elicited strong immune responses. In the present study, we generated T cell receptor‐engineered T cells (TCR‐T cells) directed against the PBF peptide (PBF TCR‐T cells). PBF TCR was successfully transduced into T cells and detected using HLA‐A*24:02/PBF peptide tetramer. PBF TCR‐T cells generated from a healthy donor were highly expanded and recognized T2‐A24 cells pulsed with PBF peptide, HLA‐A24+ 293T cells transfected with PBF cDNA, and sarcoma cell lines. To establish an adoptive cell therapy model, we modified the PBF TCR by replacing both α and β constant regions with those of mice (hybrid PBF TCR). Hybrid PBF TCR‐T cells also showed reactivity against T2‐A24 cells pulsed with PBF peptide and to HLA‐A24+ 293T cells transfected with various lengths of PBF cDNA including the PBF peptide sequence. Subsequently, we generated target cell lines highly expressing PBF (MFH03‐PBF [short] epitope [+]) containing PBF peptide with in vivo tumorigenicity. Hybrid PBF TCR‐T cells exhibited antitumor effects compared with mock T cells in NSG mice xenografted with MFH03‐PBF (short) epitope (+) cells. CD45+ T cells significantly infiltrated xenografted tumors only in the hybrid PBF TCR T cell group and most of these cells were CD8‐positive. CD8+ T cells also showed Ki‐67 expression and surrounded the CD8‐negative tumor cells expressing Ki‐67. These findings suggest that PBF TCR‐T cell therapy might be a candidate immunotherapy for sarcoma highly expressing PBF.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor

Hamada,

Tsukahara,

Watanabe

et al. 2023

Cancer Science

View full text Add to dashboard Cite

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Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma

Chen

Zhou

Zhang

et al. 2022

CBM

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INTRODUCTION: The E3 ubiquitin ligase FBXW11 exerts an oncogenic or tumor suppressive function in a cellular context-dependent manner. However, the clinical significance and biological role of FBXW11 in chondrosarcoma have not been clearly characterized. This study focuses on the expression profile, prognostic value and biological function of FBXW11 in chondrosarcoma. METHODS: FBXW11 expression was analyzed by qRT-PCR and Western blot in six cases of chondrosarcoma specimens and the matched adjacent non-tumor tissues. The expression profile and prognostic value of FBXW11 were investigated in sixty-three cases of chondrosarcoma patients. Cell viability, colony formation, migration, invasion and apoptosis assays were further detected in SW1353 chondrosarcoma cells with restored FBXW11 expression. RESULTS: Downregulation of FBXW11 was remarkably detected in human chondrosarcoma specimens compared with the corresponding non-tumor tissues and benign cartilage tumors. Downregulated FBXW11 expression significantly correlated with high-grade chondrosarcoma and poor prognosis. Furthermore, FBXW11 was identified as an independent prognostic factor for the overall survival of chondrosarcoma patients. Restored expression of FBXW11 significantly suppressed chondrosarcoma cell growth and induced apoptosis. CONCLUSIONS: These findings establish that FBXW11 was markedly downregulated and recognized as an independent prognostic factor for patients with chondrosarcoma, and restored FBXW11 expression can suppress chondrosarcoma growth and induce apoptosis, highlighting a novel biological marker and potential therapeutic target against chondrosarcoma.

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Dysregulation of Zinc Finger Protein 395 Contributes to the Pathogenesis of Chondrosarcoma

Cited by 2 publications

References 32 publications

Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor

Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor

Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma

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