2. Academic Validation
  3. OSCC-derived EVs educate fibroblasts and remodel collagen landscape

OSCC-derived EVs educate fibroblasts and remodel collagen landscape

  • Matrix Biol. 2024 Dec:134:132-143. doi: 10.1016/j.matbio.2024.10.004.
Cheng Miao 1,  Liu Liu 2,  Yubin Cao 3,  Zhishen Jiang 4,  Zhangfan Ding 1,  Yafei Chen 5,  Honglin Li 1,  Zhongkai Ma 1,  Pingchuan Ma 1,  Gaowei Zhang 1,  Longjiang Li 6,  Chunjie Li 7
Affiliations

Affiliations

  • 1 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.
  • 2 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 Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, PR China.
  • 3 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 Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, PR China. Electronic address: yubin.cao@scu.edu.cn.
  • 4 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 Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, PR China.
  • 5 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.
  • 6 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: lilongjiang@scu.edu.cn.
  • 7 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: lichunjie@scu.edu.cn.
PMID: 39393503 DOI: 10.1016/j.matbio.2024.10.004
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 COL18high COL5high 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.

Keywords

Collagen(s); Extracellular matrix (ECM); Fibroblast(s); Oral carcinogenesis; Oral oncology.

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