Wu Xinzhi, Han Xueshuai, Zhu Haibo, Li Mingxuan, Gong Lei, Jing Sicheng, Xie Weiyan, Liu Zhaoqi, Li Chuzhong, Zhang Yazhuo
Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, 100070, China.
J Exp Clin Cancer Res. 2025 Jan 27;44(1):27. doi: 10.1186/s13046-025-03296-9.
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.
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.
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.
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.
骨侵袭性垂体神经内分泌肿瘤（BI PitNETs）是垂体肿瘤的一种侵袭性亚型，其特征为骨侵袭，最终导致广泛的颅底骨破坏和碎裂。这种浸润由于可能对重要神经和动脉造成损伤，带来了重大的手术风险。然而，PitNETs引起骨侵袭的机制仍不清楚，临床实践中也缺乏针对PitNETs诱导的骨侵袭的有效干预措施。
在本研究中，我们对10例骨侵袭性PitNETs和5例非骨侵袭性PitNETs（非BI PitNETs）进行了单细胞（n = 87,287）RNA测序。我们鉴定了各种细胞类型，并通过细胞间通讯分析确定了它们之间的相互作用，该分析进一步通过实验得到验证。
我们鉴定出一种新型的TNF-α TAM巨噬细胞亚群。BI PitNETs显示出IL-34分泌增加，通过IL34/CSF1R轴影响TNF-α TAMs，导致TNF-α产生。反过来，TNF-α TAMs与CD14单核细胞通讯，促进它们分化为破骨细胞，从而导致骨侵袭。此外，我们定义了TNF-α TAM的基因特征，以指导BI PitNETs的临床预后预测。
我们的研究阐明了骨侵袭中肿瘤微环境的变化，并确定了TNF-α TAMs在促进PitNETs骨侵袭中的关键作用，为开发针对BI PitNETs的新分子标志物或治疗药物奠定了基础。
