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Far-Red Fluorescent Senescence-Associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry
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Senescent tumor cells building three-dimensional tumor clusters.

Hyun-Gyu Lee1, June Hoan Kim2, Woong Sun2

  • 1Department of Physics, Korea University, Seoul, 02841, Korea.

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Senescent cells in breast cancer colonies surprisingly aggregate nearby non-senescent cells, forming localized 3D clusters. This phenomenon is explained by biophysical factors like cell rounding and differential attachments.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Cancer Research

Background:

  • Cellular senescence is a permanent cell-cycle arrest with incompletely understood biological roles.
  • Senescent cells can influence their surrounding tissue microenvironment.
  • Tumor cells, including breast cancer cells, can undergo senescence.

Purpose of the Study:

  • To investigate the role of senescent cells within a breast cancer colony.
  • To observe and explain the aggregation behavior of senescent and non-senescent cells in a tumor context.
  • To model the biophysical mechanisms driving cell aggregation in tumor layers.

Main Methods:

  • Observation of senescent cells within dense breast cancer cell mono-layers.
  • Analysis of biophysical factors involved in cell-cell interactions.
  • Development and application of a cellular Potts Model to simulate aggregation dynamics.

Main Results:

  • Senescent cells act as aggregation centers for non-senescent cells in a 2D tumor layer.
  • Localized 3D cell-clusters are actively formed around senescent cells.
  • The model successfully recapitulated the observed aggregation phenomenon using key biophysical factors.

Conclusions:

  • Senescent cells play an active role in organizing non-senescent tumor cells.
  • Biophysical mechanisms including mitotic cell-rounding, differential cell attachments, and chemotaxis drive cluster formation.
  • Cellular Potts Model provides a framework for understanding emergent multicellular behaviors in tumors.