Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors
Abstract Background Bone-invasive Pituitary Neuroendocrine Tumors (BI PitNETs) epitomize an aggressive subtype of pituitary tumors characterized by bone invasion, culminating in extensive skull base bone destruction and fragmentation. This infiltration poses a significant surgical risk due to potent...
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BMC
2025-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03296-9 |
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| author | Xinzhi Wu Xueshuai Han Haibo Zhu Mingxuan Li Lei Gong Sicheng Jing Weiyan Xie Zhaoqi Liu Chuzhong Li Yazhuo Zhang |
| author_facet | Xinzhi Wu Xueshuai Han Haibo Zhu Mingxuan Li Lei Gong Sicheng Jing Weiyan Xie Zhaoqi Liu Chuzhong Li Yazhuo Zhang |
| author_sort | Xinzhi Wu |
| collection | DOAJ |
| description | Abstract Background Bone-invasive Pituitary Neuroendocrine Tumors (BI PitNETs) epitomize an aggressive subtype of pituitary tumors characterized by bone invasion, culminating in extensive skull base bone destruction and fragmentation. This infiltration poses a significant surgical risk due to potential damage to vital nerves and arteries. However, the mechanisms underlying bone invasion caused by PitNETs remain elusive, and effective interventions for PitNET-induced bone invasion are lacking in clinical practice. Methods In this study, we performed single-cell (n = 87,287) RNA sequencing on 10 cases of bone-invasive PitNETs and 5 cases of non-bone-invasion PitNETs (Non-BI PitNETs). We identified various cell types and determined their interactions through cell-cell communication analysis, which was further validated experimentally. Results We identified a novel TNF-α+ TAM macrophage subset. BI PitNETs showed increased IL-34 secretion, impacting TNF-α+ TAMs via the IL34/CSF1R axis, leading to TNF-α production. TNF-α+ TAMs, in turn, communicate with CD14 + monocytes to promote their differentiation into osteoclasts and leading to bone invasion. In addition, we defined a gene signature for TNF-α+ TAM to guide the clinical prognosis prediction of BI PitNETs. Conclusions Our study elucidates the tumor microenvironment changes in bone invasion and identifies the critical role of TNF-α+ TAMs in promoting bone invasion of PitNETs, laying a foundation for developing new molecular markers or therapeutic agents targeting BI PitNETs. |
| format | Article |
| id | doaj-art-7b4a4ce6591a4bc3a6bfd8074380b300 |
| institution | Kabale University |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-7b4a4ce6591a4bc3a6bfd8074380b3002025-02-02T12:47:45ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-01-0144111510.1186/s13046-025-03296-9Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumorsXinzhi Wu0Xueshuai Han1Haibo Zhu2Mingxuan Li3Lei Gong4Sicheng Jing5Weiyan Xie6Zhaoqi Liu7Chuzhong Li8Yazhuo Zhang9Beijing Neurosurgical Institute, Capital Medical UniversityBeijing Institute of Genomics, China National Center for Bioinformation, Chinese Academy of SciencesDepartment of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityDepartment of Biology, University of California San DiegoBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Institute of Genomics, China National Center for Bioinformation, Chinese Academy of SciencesBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityAbstract Background Bone-invasive Pituitary Neuroendocrine Tumors (BI PitNETs) epitomize an aggressive subtype of pituitary tumors characterized by bone invasion, culminating in extensive skull base bone destruction and fragmentation. This infiltration poses a significant surgical risk due to potential damage to vital nerves and arteries. However, the mechanisms underlying bone invasion caused by PitNETs remain elusive, and effective interventions for PitNET-induced bone invasion are lacking in clinical practice. Methods In this study, we performed single-cell (n = 87,287) RNA sequencing on 10 cases of bone-invasive PitNETs and 5 cases of non-bone-invasion PitNETs (Non-BI PitNETs). We identified various cell types and determined their interactions through cell-cell communication analysis, which was further validated experimentally. Results We identified a novel TNF-α+ TAM macrophage subset. BI PitNETs showed increased IL-34 secretion, impacting TNF-α+ TAMs via the IL34/CSF1R axis, leading to TNF-α production. TNF-α+ TAMs, in turn, communicate with CD14 + monocytes to promote their differentiation into osteoclasts and leading to bone invasion. In addition, we defined a gene signature for TNF-α+ TAM to guide the clinical prognosis prediction of BI PitNETs. Conclusions Our study elucidates the tumor microenvironment changes in bone invasion and identifies the critical role of TNF-α+ TAMs in promoting bone invasion of PitNETs, laying a foundation for developing new molecular markers or therapeutic agents targeting BI PitNETs.https://doi.org/10.1186/s13046-025-03296-9PitNETsBone invasionTAMTNF-αMacrophage |
| spellingShingle | Xinzhi Wu Xueshuai Han Haibo Zhu Mingxuan Li Lei Gong Sicheng Jing Weiyan Xie Zhaoqi Liu Chuzhong Li Yazhuo Zhang Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors Journal of Experimental & Clinical Cancer Research PitNETs Bone invasion TAM TNF-α Macrophage |
| title | Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| title_full | Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| title_fullStr | Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| title_full_unstemmed | Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| title_short | Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| title_sort | single cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors |
| topic | PitNETs Bone invasion TAM TNF-α Macrophage |
| url | https://doi.org/10.1186/s13046-025-03296-9 |
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