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Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured

Yuka Aizawa1,2, Kenta Haga3, Nagako Yoshiba4

  • 1Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Biomedicines
|October 26, 2024
PubMed
Summary

We created a 3D organotypic culture model for oral squamous cell carcinoma (OSCC) to mimic the tumor microenvironment. This model accurately represents oral cancer tissue, aiding in understanding tumor behavior and treatment response.

Keywords:
3D in vitro modelcancer-associated fibroblastsoral canceroral mucosaorganotypic culturepatient-derivedpolarity

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • 3D Cell Culture Models

Background:

  • Three-dimensional (3D) organoids are crucial for studying tumor heterogeneity and predicting treatment outcomes.
  • Oral squamous cell carcinoma (OSCC) research benefits from models that recapitulate its complex tumor-stromal interface.

Purpose of the Study:

  • To develop a 3D organotypic culture model of OSCC.
  • To replicate the tumor-stromal interface by co-culturing OSCC cells with patient-derived cancer-associated fibroblasts (PD-CAFs).

Main Methods:

  • Utilized a stainless-steel ring to establish distinct cancer stroma and OSCC layers.
  • Constructed a bi-layered model mimicking oral cancer tissue architecture within the oral mucosa.
  • Co-cultured four cell types, including PD-CAFs, to simulate the tumor microenvironment.

Main Results:

  • Demonstrated close proximity and suggested crosstalk between α-smooth muscle actin-positive PD-CAFs and the OSCC layer.
  • Observed a lack of linear laminin-γ2 expression at the OSCC-stroma interface, indicating basement membrane disruption.
  • Validated the model's ability to mimic in vivo oral cancer 3D architecture and polarity.

Conclusions:

  • The developed 3D organotypic model accurately mimics the oral cancer tumor microenvironment (TME).
  • This model's in vivo-like architecture is vital for elucidating oral cancer TME dynamics.
  • The model offers a valuable platform for advancing oral cancer research and therapeutic strategies.