Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood.
Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.
iScience. 2024 Sep 11*** epublish ***
Weipu Mao, Kangjie Xu, Keyi Wang, Houliang Zhang, Jie Ji, Jiang Geng, Si Sun, Chaoming Gu, Atrayee Bhattacharya, Cheng Fang, Tao Tao, Ming Chen, Jianping Wu, Shuqiu Chen, Chao Sun, Bin Xu
Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China., Central Laboratory Department, Binhai County People's Hospital, Yancheng 224000, China., Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China., Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39386756