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Updated: Mar 29, 2026
Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
CXCR4+ cells in NPC tumor sphere have metastatic potential
Zhenwei Zhu1, Jingyu Li2, Jingxian Liu3
1Shenzhen Hospital of Southern Medical University, Department of Oncology, Shenzhen, P.R. China; Southern Medical University, School of Basic Medical Sciences, Cancer Research Institute, Key Laboratory of Tumor Immunology Research, Guangzhou, P.R. China.
Objective:
Nasopharyngeal Carcinoma (NPC) tumor stem cells play a crucial role in the occurrence and development of nasopharyngeal carcinoma, but the identity and role of Cancer Stem Cell (CSC) subpopulations that drive metastasis remain unclear. This study explores the mechanisms of NPC stem cell subpopulations (CXCR4+) in the development of NPC, providing a reference for therapeutic targets for NPC.
Methods:
Immunohistochemical analysis of CXCR4 expression was performed in 71 NPC and 5 chronic nasopharyngitis tissues. Stemness, tumorigenicity and Epithelial-Mesenchymal Transition (EMT) profiles were established for cells in tumor spheres by flow cytometry (CD133/CXCR4), functional assays, Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) and Western blotting. CXCR4+ cell metastatic potential was evaluated in a mouse NPC model.
Results:
CXCR4 expression correlated with NPC T and N stage. CD133+ and CXCR4+ cells were enriched in the tumor sphere. CXCR4+ subsets had enhanced self-renewal (The CXCR4-positive subgroup exhibited a 45% increase in the ability to form tumor spheres), spindle morphology and migration/invasion with upregulation of markers of EMT, Snail, Twist, Vimentin, N-cadherin, stemness, Oct4, Nanog, Sox2 and downregulation of E-cadherin. CXCR4+ tumorsphere cells potentiated metastatic lung nodules in vivo via SDF-1/CXCR4 signaling, giving a 500% increase relative to controls.
Conclusion:
A metastatic CSC subpopulation present in NPC express CXCR4 and have activated EMT and SDF-1/CXCR4-driven metastasis. CXCR4 may have utility as a biomarker and the SDF-1/CXCR4 axis may be a therapeutic target for NPC.
