GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma
Understanding metastatic osteosarcoma relies on defining the complexity of cell types, their associated molecular profiles, and interactions among cells in the tumor microenvironment. Here, we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly e...
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225000807 |
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| author | Linzhu Wang Wenyue Li Weihang Ji Danyang Bing Mingyue Liu Kaidong Liu Bo Chen Zhangxiang Zhao Yunyan Gu Xuelian Li Xiaoqiang E Lei Yang |
| author_facet | Linzhu Wang Wenyue Li Weihang Ji Danyang Bing Mingyue Liu Kaidong Liu Bo Chen Zhangxiang Zhao Yunyan Gu Xuelian Li Xiaoqiang E Lei Yang |
| author_sort | Linzhu Wang |
| collection | DOAJ |
| description | Understanding metastatic osteosarcoma relies on defining the complexity of cell types, their associated molecular profiles, and interactions among cells in the tumor microenvironment. Here, we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+ osteoblasts (OB). Under the regulation of E2F family members, GTSE1+ OB cells harbored enhanced proliferation activity and high differentiation potential. Augmentation of GTSE1 enhanced the abilities of cell migration and invasion, while silencing of GTSE1 impaired the abilities in human OB cell lines. Furthermore, cellular communication analysis showed the cross-talk between GTSE1+ OB cells and CD8+ T cells in metastasis was achieved through the MIF-(CD74-CXCR4) pair. Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma. Correlation analysis unveiled that GTSE1+ OB cells and monocytes were the negatively correlated populations at the single-cell level, a finding validated in 4 independent osteosarcoma datasets comprising 226 samples. Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+ OB cells. |
| format | Article |
| id | doaj-art-81178f8279cb4424a4874fcd40bba113 |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-81178f8279cb4424a4874fcd40bba1132025-08-24T05:13:01ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610159110.1016/j.gendis.2025.101591GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcomaLinzhu Wang0Wenyue Li1Weihang Ji2Danyang Bing3Mingyue Liu4Kaidong Liu5Bo Chen6Zhangxiang Zhao7Yunyan Gu8Xuelian Li9Xiaoqiang E10Lei Yang11Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaClinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou, Chongqing 404100, ChinaDepartment of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; Corresponding author.Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; Key Laboratory of Hepatosplenic Surgery of Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China; Corresponding author. Department of Orthopedics; Key Laboratory of Hepatosplenic Surgery of Ministry of Education; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.Understanding metastatic osteosarcoma relies on defining the complexity of cell types, their associated molecular profiles, and interactions among cells in the tumor microenvironment. Here, we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+ osteoblasts (OB). Under the regulation of E2F family members, GTSE1+ OB cells harbored enhanced proliferation activity and high differentiation potential. Augmentation of GTSE1 enhanced the abilities of cell migration and invasion, while silencing of GTSE1 impaired the abilities in human OB cell lines. Furthermore, cellular communication analysis showed the cross-talk between GTSE1+ OB cells and CD8+ T cells in metastasis was achieved through the MIF-(CD74-CXCR4) pair. Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma. Correlation analysis unveiled that GTSE1+ OB cells and monocytes were the negatively correlated populations at the single-cell level, a finding validated in 4 independent osteosarcoma datasets comprising 226 samples. Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+ OB cells.http://www.sciencedirect.com/science/article/pii/S2352304225000807GTSE1MetastasisOsteosarcomaSingle-cell transcriptomeTumor microenvironment |
| spellingShingle | Linzhu Wang Wenyue Li Weihang Ji Danyang Bing Mingyue Liu Kaidong Liu Bo Chen Zhangxiang Zhao Yunyan Gu Xuelian Li Xiaoqiang E Lei Yang GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma Genes and Diseases GTSE1 Metastasis Osteosarcoma Single-cell transcriptome Tumor microenvironment |
| title | GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma |
| title_full | GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma |
| title_fullStr | GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma |
| title_full_unstemmed | GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma |
| title_short | GTSE1-expressed osteoblastic cells facilitate formation of pro-metastatic tumor microenvironment in osteosarcoma |
| title_sort | gtse1 expressed osteoblastic cells facilitate formation of pro metastatic tumor microenvironment in osteosarcoma |
| topic | GTSE1 Metastasis Osteosarcoma Single-cell transcriptome Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225000807 |
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