OSCC-derived EVs educate fibroblasts and remodel collagen landscape.

Matrix Biol

State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, PR China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, PR China. Electronic address:

Published: December 2024

AI Article Synopsis

  • Cancer-associated myofibroblasts (mCAFs) play a crucial role in the tumor microenvironment by altering the extracellular matrix (ECM), particularly in oral squamous cell carcinoma (OSCC).
  • This study found that extracellular vesicles (EVs) from OSCC enhance the conversion of fibroblasts into mCAFs, promoting tumor invasion through specific collagen type enrichment.
  • The research reveals that TGF-β1 in EVs activates the TGF-β1/Smad3 pathway, suggesting that targeting this signaling could be a promising therapeutic approach for OSCC.

Article Abstract

Cancer-associated myofibroblasts (mCAFs) represent a significant component of the tumor microenvironment due to their contributions to extracellular matrix (ECM) remodeling. The pro-tumor mechanisms of extracellular vesicles (EVs) by regulating mCAFs and related collagens remain poorly understood in oral squamous cell carcinoma (OSCC). In this study, through analysis of single-cell sequencing data and immunofluorescence staining, we confirmed the increased presence of mCAFs and enrichment of specific collagen types in OSCC tissues. Furthermore, we demonstrated that OSCC-derived EVs promote the transformation of fibroblasts into mCAFs, leading to tumor invasion. Proteomic analysis identified the presence of TGF-β1 in EVs and revealed its role in inducing mCAFs via the TGF-β1/SMAD signaling pathway. Experiments in vivo confirmed that EVs, particularly those carrying TGF-β1, trigger COL18 COL5 matrix deposition, thereby forming the pro-tumor ECM in OSCC. In summary, our investigation unveils the significant involvement of OSCC-derived EVs in orchestrating the differentiation of fibroblasts into mCAFs and modulating specific collagen types within the ECM. Therefore, this study provides a theoretical basis for targeting the EV-mediated TGF-β1 signaling pathway as a potential therapeutic strategy for OSCC.

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http://dx.doi.org/10.1016/j.matbio.2024.10.004DOI Listing

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OSCC-derived EVs educate fibroblasts and remodel collagen landscape.

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State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, PR China; Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, PR China. Electronic address:

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  • This study found that extracellular vesicles (EVs) from OSCC enhance the conversion of fibroblasts into mCAFs, promoting tumor invasion through specific collagen type enrichment.
  • The research reveals that TGF-β1 in EVs activates the TGF-β1/Smad3 pathway, suggesting that targeting this signaling could be a promising therapeutic approach for OSCC.
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