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Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model
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Tumor-Tissue Boundaries as Instructive Interfaces in Breast Cancer Cell Invasion.

Cornelia Clemens1, Thomas Zerjatke2, Andrine Frank1

  • 1Institute of Biochemistry, Leipzig University, 04103, Leipzig, Germany.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 11, 2025
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Summary
This summary is machine-generated.

Metastatic cancer cells change behavior at tissue boundaries. This study shows boundaries instruct all cells to become more invasive, not just select cancer stem cells, offering new therapeutic targets.

Keywords:
breast cancer cellscell migrationextracellular matrix interfacesinstructive phenotype switching

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Area of Science:

  • Oncology
  • Cell Biology
  • Biophysics

Background:

  • Metastatic cancer cells must cross tissue boundaries, facing structural and biochemical challenges.
  • Phenotypic changes, including increased invasiveness, occur in breast cancer cells after migrating through tumor-stromal boundaries.
  • It's debated whether these changes result from selective filtering of subpopulations or an instructive cellular response.

Purpose of the Study:

  • To investigate whether tumor-tissue boundaries selectively filter cancer cell subpopulations or instructively alter cell behavior.
  • To determine the mechanism driving phenotypic changes in cancer cells at tissue interfaces.

Main Methods:

  • Single-cell migration analysis in a 3D collagen matrix model.
  • Analysis of cell proliferation heterogeneity.
  • Computational modeling of cell behavior at interfaces.

Main Results:

  • All cancer cells, not just specific subpopulations, successfully transmigrated the tumor-tissue interface.
  • No evidence of selective filtering of pre-existing subpopulations like cancer stem cells was found.
  • Proliferation heterogeneity remained consistent between transmigrated and non-transmigrated cells, supporting an instructive mechanism.

Conclusions:

  • Tumor-tissue boundaries act as instructive interfaces that reprogram cancer cell phenotypes.
  • This reprogramming enhances cancer cell invasiveness and aggressiveness during metastasis.
  • Tissue boundaries represent a potentially targetable mechanism in metastatic progression.