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Related Experiment Video

Updated: May 19, 2026

Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
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Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography

Published on: August 16, 2020

Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function.

Ioannis K Zervantonakis1, Shannon K Hughes-Alford, Joseph L Charest

  • 1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 8, 2012
PubMed
Summary

Tumor cell intravasation, a key step in metastasis, is regulated by the tumor microenvironment. Macrophage signaling impairs endothelial barrier function, increasing tumor cell entry into the bloodstream.

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Area of Science:

  • Oncology
  • Cell Biology
  • Biomedical Engineering

Background:

  • Cancer metastasis involves tumor cell entry into the bloodstream.
  • Mechanisms of cancer cell intravasation are not fully understood.
  • The tumor-vascular interface is critical for metastasis.

Purpose of the Study:

  • To investigate the regulation of cancer cell intravasation.
  • To test the hypothesis that biochemical factors and macrophage interactions influence intravasation.
  • To quantify endothelial barrier function and tumor cell migration dynamics.

Main Methods:

  • Developed a 3D microfluidic assay to mimic the tumor-vascular interface.
  • Quantified endothelial permeability and barrier function.
  • Utilized live imaging to observe tumor cell intravasation and tumor-endothelial cell interactions.
  • Investigated the role of tumor necrosis factor alpha (TNF-α) secreted by macrophages.

Main Results:

  • Macrophage signaling via TNF-α impairs endothelial barrier function.
  • Impaired endothelial barrier function increases tumor cell intravasation rates.
  • Endothelial barrier impairment correlates with increased and faster tumor-endothelial cell interactions.
  • Fibrosarcoma cell intravasation dynamics were studied under varying barrier conditions.

Conclusions:

  • The endothelium acts as a barrier to tumor cell intravasation.
  • Factors within the tumor microenvironment, such as macrophage-secreted TNF-α, can regulate this endothelial barrier.
  • Understanding these interactions is crucial for developing anti-metastatic therapies.