Wang Linzhu, Li Wenyue, Ji Weihang, Bing Danyang, Liu Mingyue, Liu Kaidong, Chen Bo, Zhao Zhangxiang, Gu Yunyan, Li Xuelian, E Xiaoqiang, Yang Lei
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Genes Dis. 2025 Mar 7;12(6):101591. doi: 10.1016/j.gendis.2025.101591. eCollection 2025 Nov.
Understanding metastatic osteosarcoma relies on defining the complexity of cell types, their associated molecular profiles, and interactions among cells in the tumor microenvironment. Here, we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for osteoblasts (OB). Under the regulation of E2F family members, OB cells harbored enhanced proliferation activity and high differentiation potential. Augmentation of enhanced the abilities of cell migration and invasion, while silencing of impaired the abilities in human OB cell lines. Furthermore, cellular communication analysis showed the cross-talk between OB cells and CD8 T cells in metastasis was achieved through the -(-) pair. Spatial transcriptomic data revealed that - and -/ showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma. Correlation analysis unveiled that OB cells and monocytes were the negatively correlated populations at the single-cell level, a finding validated in 4 independent osteosarcoma datasets comprising 226 samples. Our findings suggest that overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting OB cells.
了解转移性骨肉瘤依赖于明确细胞类型的复杂性、其相关的分子特征以及肿瘤微环境中细胞间的相互作用。在此，我们整合了单细胞和批量基因表达数据集，并揭示转移性病变中富含成骨细胞（OB）。在E2F家族成员的调控下，OB细胞具有增强的增殖活性和高分化潜能。增强 可提高细胞迁移和侵袭能力，而在人OB细胞系中沉默 则会损害这些能力。此外，细胞通讯分析表明，转移过程中OB细胞与CD8 T细胞之间的相互作用是通过 -(-) 对实现的。空间转录组数据显示，在未分化多形性肉瘤中， - 和 -/ 的正相关性高于平滑肌肉瘤。相关性分析表明，在单细胞水平上，OB细胞和单核细胞是负相关群体，这一发现已在包含226个样本的4个独立骨肉瘤数据集中得到验证。我们的研究结果表明， 过表达可作为骨肉瘤转移的潜在生物标志物，并为通过靶向OB细胞预防转移提供了一种有前景的策略。
