Tang Haijun, Cai Yangjie, Yang Mingxiu, Tang Shengping, Huang Qian, Li Hening, Liu Shangyu, Teng Hongcai, Xie Tianyu, He Maolin, Liu Yun, Liao Shijie
Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Traumatic Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
NPJ Precis Oncol. 2025 Apr 13;9(1):104. doi: 10.1038/s41698-025-00896-8.
Osteosarcoma, the most common primary malignant bone tumor in children and adolescents, is highly aggressive and prone to metastasis. Endothelial cells (ECs) are involved in angiogenesis and play a key role in promoting the metastasis of tumor. However, research on tip-like ECs within osteosarcoma was extremely rare. In this study, a single-cell atlas of ECs was constructed using single-cell transcriptomic data. It was found that tip-like ECs were abundant in the primary tumors and metastatic foci. Gene sets score analysis indicated their enrichment in pathways associated with angiogenesis and metastasis. What's more, MCAM was highly expressed in tip-like ECs and was likely to promote the metastasis of osteosarcoma. MCAM was also found to be highly expressed in the ECs of metastatic lymph nodes when compared to normal lymph node samples. Meanwhile, spatial transcriptomics data confirmed the presence of MCAM-positive ECs in metastatic lymph node, closely localized to osteoblasts. In vitro assays, including qRT-PCR, tube formation, and immunofluorescence, validated the role of the MCAM gene in promoting angiogenesis. In conclusion, tip-like ECs may promote tumor metastasis by enhancing angiogenesis. MCAM was a functional gene for tip-like ECs and could serve as a target for the treatment of osteosarcoma.
骨肉瘤是儿童和青少年中最常见的原发性恶性骨肿瘤，具有高度侵袭性且易于转移。内皮细胞（ECs）参与血管生成，并在促进肿瘤转移中起关键作用。然而，关于骨肉瘤中类顶端内皮细胞的研究极为罕见。在本研究中，利用单细胞转录组数据构建了内皮细胞的单细胞图谱。研究发现，类顶端内皮细胞在原发性肿瘤和转移灶中大量存在。基因集评分分析表明它们在与血管生成和转移相关的通路中富集。此外，MCAM在类顶端内皮细胞中高表达，可能促进骨肉瘤转移。与正常淋巴结样本相比，MCAM在转移淋巴结的内皮细胞中也高表达。同时，空间转录组学数据证实转移淋巴结中存在MCAM阳性内皮细胞，且与成骨细胞紧密相邻。体外实验，包括qRT-PCR、管腔形成和免疫荧光，验证了MCAM基因在促进血管生成中的作用。总之，类顶端内皮细胞可能通过增强血管生成促进肿瘤转移。MCAM是类顶端内皮细胞的一个功能基因，可作为骨肉瘤治疗的靶点。
