CXCR4+ cells in NPC tumor sphere have metastatic potential.

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.