Single-cell analysis reveals CD34+CD90+ endothelial cells promote tumor metastasis in gallbladder cancer

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract, with high metastasis incidence and extremely low survival rate. The tumor endothelial cells (TECs) are fundamental components in the tumor microenvironment and significantly contribute to various tumor progression; however,...

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Published inNPJ precision oncology Vol. 9; no. 1; pp. 242 - 12
Main Authors Hou, Minghui, Chen, Jianan, Jiang, Youhai, Liu, Chunliang, Wang, Xiang, Liu, Erdong, Zong, Yali, Gu, Mingye, Meng, Zhengyuan, Wang, Senyan, Wei, Wenjuan, Liu, Qi, Wang, Hongyang, Fu, Jing, Zhao, Xiaofang
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 18.07.2025
Nature Publishing Group
Nature Portfolio
Subjects
692/699/67/322
692/699/67/327
Cancer Research
Cell growth
Extracellular matrix
Flow cytometry
Gallbladder cancer
Gene Therapy
Genes
Human Genetics
Immunoglobulins
Internal Medicine
Medical prognosis
Medicine
Medicine & Public Health
Metastasis
Oncology
Patients
Survival analysis
Vascular endothelial growth factor
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Summary:Gallbladder cancer (GBC) is the most common malignancy of the biliary tract, with high metastasis incidence and extremely low survival rate. The tumor endothelial cells (TECs) are fundamental components in the tumor microenvironment and significantly contribute to various tumor progression; however, the roles of TECs in GBC are poorly understood. Here, using single-cell RNA sequencing, we identify a GBC-enriched endothelial population-CD34 + CD90 + ECs (SAEndo2). The CD34 + CD90 + endothelial subset correlates with patients’ poor prognosis and liver metastasis. In vitro and in vivo experiments suggest that CD34 + CD90 + ECs promote the GBC cell migration and metastasis, showing EndoMT properties. Moreover, CD34 + CD90 + ECs display enhanced activation of TGF-β signaling, and TGF-β inhibition abolishes the CD34 + CD90 + ECs’ promotion effect on GBC cell migration. Collectively, our study provides a detailed profiling of endothelial cells in GBC and identifies an essential endothelial population that regulates GBC metastasis, laying new theoretical insight and offering a potential therapeutic target for GBC metastasis.
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ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-025-01040-2