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.2024.10.004 | DOI Listing |
Matrix Biol
December 2024
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:
Front Cell Dev Biol
September 2023
Department of Integrative Oncology, British Columbia Cancer Research Center, Vancouver, BC, Canada.
Int Immunopharmacol
May 2023
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address:
Background: Inflammatory cytokines in the tumor microenvironment (TME) contribute to tumor growth, proliferation, and invasion, and tumor-derived extracellular vesicles (EVs) act as critical "messengers" of communication in the tumor microenvironment. The effects of EVs derived from oral squamous cell carcinoma (OSCC) cells on tumor progression and the inflammatory microenvironment are still unclear. Our study aims to investigate the role of OSCC-derived EVs in tumor progression, the imbalanced TME, and immunosuppression and their effect on the IL-17A-induced signaling pathway.
View Article and Find Full Text PDFInt J Mol Sci
February 2020
Melbourne Dental School, The University of Melbourne, 720 Swanston Street, Carlton, VIC 3053, Australia.
Extracellular vesicles (EVs) are secreted from most cell types and utilized in a complex network of near and distant cell-to-cell communication. Insight into this complex nanoscopic interaction in the development, progression and treatment of oral squamous cell carcinoma (OSCC) and precancerous oral mucosal disorders, termed oral potentially malignant disorders (OPMDs), remains of interest. In this review, we comprehensively present the current state of knowledge of EVs in OSCC and OPMDs.
View Article and Find Full Text PDFOral Oncol
November 2018
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations.
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