Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target

摘要: Epithelial-mesenchymal transition (EMT) is a key contributor in tumor progression and metastasis. EMT produces cellular heterogeneity within head neck squamous cell carcinomas (HNSCC) by creating phenotypically distinct mesenchymal subpopulation that resistant to conventional therapies. In this study, we systematically characterized differences the secretomes of E-cadherin high epithelial-like low mesenchymal-like subpopulations using unbiased targeted proteomics. A total 1765 proteins showed significant changes with 177 elevated epithelial 173 cells. Key nodes affected networks included NFκB, Akt, ERK, most implicated components involved various aspects extracellular matrix. particular, large were observed multiple collagens at much higher abundance levels subpopulation. These cells also exhibited secretome profile resembling cancer-associated fibroblastic (CAF). S100A4, commonly used marker for cells, was more than 20-fold increase further verified transcriptome level. S100A4 known mediator EMT, leading metastasis has been proposed as potential source solid tumors. knockdown small interfering RNA led decreased expression, secretion activity matrix metalloproteinase 2, quantitative PCR, reaction monitoring zymography analyses, reduced invasion collagen-embedded spheroids. Further confirmation three-dimensional organotypic reconstructs less advanced differentiation interference samples. Orthotopic model, developed validate findings vivo, demonstrated decrease spontaneous augmented primary siS100A4 xenografts. results demonstrate value profiling evaluate phenotypic conversion identify novel therapeutic targets such S100A4.