Related Experiment Video
Updated: May 30, 2025
A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary
Xinzhi Wu1,2, Xueshuai Han3, Haibo Zhu2
1Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
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.
