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Related Experiment Video

Updated: Nov 8, 2025

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis
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Tumor cell nuclei soften during transendothelial migration.

Anya B Roberts1, Jitao Zhang2, Vijay Raj Singh3

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

Journal of Biomechanics
|April 21, 2021
PubMed
Summary

Cancer cells soften their nuclei and cell bodies to squeeze through blood vessels during metastasis. This mechanical change aids tumor cell extravasation and spread.

Keywords:
Brillouin microscopyCell modulusInterference microscopyMetastasis

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Area of Science:

  • Biophysics
  • Cancer Biology
  • Cell Mechanics

Background:

  • Cancer metastasis involves tumor cells deforming to pass through blood vessel walls.
  • Nuclear stiffness is crucial for transendothelial migration, but its changes during this process are unknown.

Purpose of the Study:

  • To investigate changes in tumor cell and nuclear mechanical properties during transendothelial migration.
  • To determine if tumor cells alter stiffness to facilitate extravasation.

Main Methods:

  • Utilized Brillouin confocal microscopy (BCM) and confocal reflectance quantitative phase microscopy (QPM).
  • Non-contact imaging tracked mechanical properties of live, transmigrating tumor cells (MDA-MB-231, A549, A375) in an in vitro collagen gel.
  • Monitored changes in cell and nuclear stiffness during extravasation.

Main Results:

  • Both tumor cells and their nuclei exhibited decreased stiffness (softening) upon extravasation.
  • The softened state of the nuclear membrane persisted for at least 24 hours post-migration.
  • Observed softening in multiple cancer cell lines (MDA-MB-231, A549, A375).

Conclusions:

  • Tumor cells dynamically adjust their mechanical properties, specifically softening, to facilitate extravasation.
  • This mechanical plasticity is a key adaptation for cancer cells during the metastatic process.
  • Findings provide insights into the physical mechanisms underlying cancer cell migration.