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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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-025-03296-9 |
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| Summary: | 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. |
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| ISSN: | 1756-9966 |