单位：[1]Sino-German Neuro-Oncology Molecular Laboratory,Department of Neurosurgery,Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology,Jiefang Avenue 1095,Wuhan 430030,China外科学系肿瘤科科研平台神经外科中德分子神经肿瘤实验室华中科技大学同济医学院附属同济医院[2]Department of Orthopedics,Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology,Jiefang Avenue 1095,Wuhan 430030,China华中科技大学同济医学院附属同济医院外科学系骨科
Simple Summary Pituitary adenoma (PA) bone invasion seriously affects patient prognosis, and its mechanism needs more investigation. Through exploring the interaction between PA tumor cells and osteoclasts, we have revealed an essential theory of the progression of PA bone invasion. Localized inflammatory environment in PAs was identified as a feature of bone invasion. In this study, we identified PKC theta as a key signal for PA bone invasion, and PAs release IL-1 beta via the PKC theta/NF-kappa B/IL-1 beta pathway to induce monocyte-osteoclast differentiation in a paracrine manner. Meanwhile, we also found that celastrol, as a natural product, can obviously reduce the secretion of IL-1 beta as well as alleviate the progression of bone invasion, which is promising for clinical application. Background: Pituitary adenoma (PA) bone invasion results in adverse outcomes, such as reduced rates of complete surgical resection and biochemical remission as well as increased recurrence rates, though few studies have been conducted. Methods: We collected clinical specimens of PAs for staining and statistical analysis. Evaluation of the ability of PA cells to induce monocyte-osteoclast differentiation by coculturing PA cells with RAW264.7 in vitro. An in vivo model of bone invasion was used to simulate the process of bone erosion and evaluate the effect of different interventions in alleviating bone invasion. Results: We found an overactivation of osteoclasts in bone-invasive PAs and concomitant aggregation of inflammatory factors. Furthermore, activation of PKC theta in PAs was established as a central signaling promoting PA bone invasion through the PKC theta/NF-kappa B/IL-1 beta pathway. By inhibiting PKC theta and blocking IL1 beta, we were able to significantly reverse bone invasion in an in vivo study. Meanwhile, we also found that celastrol, as a natural product, can obviously reduce the secretion of IL-1 beta as well as alleviate the progression of bone invasion. Conclusions: By activating the PKC theta/NF-kappa B/IL-1 beta pathway, pituitary tumors are able to induce monocyte-osteoclast differentiation in a paracrine manner and promote bone invasion, which can be alleviated by celastrol.
基金：
National Nature Science Foundation of China [82173136]
第一作者单位：[1]Sino-German Neuro-Oncology Molecular Laboratory,Department of Neurosurgery,Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology,Jiefang Avenue 1095,Wuhan 430030,China
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推荐引用方式(GB/T 7714)：
Wang Quanji,Lei Zhuowei,Wang Zihan,et al.PKC theta Regulates Pituitary Adenoma Bone Invasion by Activating Osteoclast in NF-kappa B/IL-1 beta-Dependent Manner[J].CANCERS.2023,15(5):doi:10.3390/cancers15051624.
APA：
Wang, Quanji,Lei, Zhuowei,Wang, Zihan,Jiang, Qian,Zhang, Zhuo...&Lei, Ting.(2023).PKC theta Regulates Pituitary Adenoma Bone Invasion by Activating Osteoclast in NF-kappa B/IL-1 beta-Dependent Manner.CANCERS,15,(5)
MLA：
Wang, Quanji,et al."PKC theta Regulates Pituitary Adenoma Bone Invasion by Activating Osteoclast in NF-kappa B/IL-1 beta-Dependent Manner".CANCERS 15..5(2023)
医学