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Multimodal Phasor Approach to Study Breast Cancer Cell Invasion in a 3D Spheroid Model.

Giulia Tedeschi1, Francesco Palomba1, Lorenzo Scipioni1

  • 1Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, Irvine, California 92617, United States.

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|August 1, 2025
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This study used advanced imaging to track how triple-negative breast cancer cells invade tissue and change. Researchers observed and quantified cancer cell plasticity in response to environmental shifts.

Keywords:
ECMSpheroidsbreast cancermetabolic imagingmultimodal microscopy

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Area of Science:

  • Biomedical Imaging
  • Cancer Biology
  • Extracellular Matrix Research

Background:

  • Cancer invasion involves complex cellular and microenvironmental changes.
  • Understanding cancer cell plasticity is crucial for developing effective therapies.
  • Current imaging techniques often lack the depth and resolution to study these processes in detail.

Purpose of the Study:

  • To investigate cancer cell invasion and physiological changes using deep-tissue imaging.
  • To model cancer cell invasion of the extracellular matrix using 3D breast cancer spheroids.
  • To analyze multiple cancer hallmarks within the same spheroid.

Main Methods:

  • Implemented a multimodal functional imaging framework for deep-tissue analysis.
  • Utilized fluorescence lifetime imaging microscopy (NADH-FLIM) for metabolic imaging.
  • Employed hyperspectral imaging (Nile Red) for lipid content and second harmonic generation (SHG) for extracellular matrix imaging.
  • Performed phasor-based bioimage analysis at multiple time points.

Main Results:

  • Quantified physiological property changes during cancer cell invasion.
  • Tracked morphological and biological properties including metabolism, fatty acid storage, and collagen organization.
  • Observed and quantified cancer cell plasticity in response to environmental composition changes.

Conclusions:

  • Multimodal deep-imaging provides a powerful framework for studying cancer invasion.
  • Cancer cell plasticity is a key factor influenced by the microenvironment.
  • This approach offers new insights into the mechanisms of cancer metastasis.