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Related Experiment Video

Updated: Jul 13, 2025

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
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Mapping Cell-in-Cell Structures in Oral Squamous Cell Carcinoma.

Leonardo de Oliveira Siquara da Rocha1,2, Bruno Solano de Freitas Souza1,3, Ricardo Della Coletta4,5

  • 1Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, BA, Brazil.

Cells
|October 13, 2023
PubMed
Summary

Cell-in-cell structures in oral squamous cell carcinoma (OSCC) spheroids were studied using a 3D bioprinting model. These structures, predominantly found in mixed cancer-associated fibroblast spheroids, may influence tumor aggressiveness.

Keywords:
cancer-associated fibroblastscell cannibalismcell-in-cell structuresoral squamous cell carcinomatumor spheroids

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Area of Science:

  • Oncology
  • Cell Biology
  • Biotechnology

Background:

  • Cell-in-cell (CIC) structures are linked to aggressive oral squamous cell carcinoma (OSCC) and poor patient outcomes.
  • Understanding the molecular mechanisms of CIC formation in OSCC requires advanced in vitro models.

Purpose of the Study:

  • To investigate cell-in-cell (CIC) structures in oral squamous cell carcinoma (OSCC) using a 3D spheroid model.
  • To analyze the formation, morphology, and location of CIC structures within the tumor microenvironment.

Main Methods:

  • Oral squamous cell carcinoma (OSCC) and cancer-associated fibroblast (CAF) cell lines were cultured into spheroids using a bioprinting system.
  • Spheroid morphology, including hypoxic and proliferative zones, was analyzed over time using microscopy and image analysis software.
  • Cell-in-cell structure occurrence, complexity, and morphology were assessed within different spheroid regions.

Main Results:

  • Well-formed spheroids mimicking the tumor microenvironment (hypoxic core, proliferative periphery) developed within 6 hours.
  • Cell-in-cell (CIC) structures were observed in both homotypic and heterotypic spheroids.
  • CIC structures were predominantly found in the proliferative zones of mixed OSCC/CAF spheroids, with instances of 'complex cannibalism' noted.

Conclusions:

  • The 3D spheroid model effectively replicates key features of the OSCC tumor microenvironment, including CIC formation.
  • This model provides a valuable platform for further research into the morphology, development, and prognostic significance of CIC structures in OSCC.