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Updated: Jul 16, 2025
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Noninvasive morpho-molecular imaging reveals early therapy-induced senescence in human cancer cells
Arianna Bresci1, Jeong Hee Kim2, Silvia Ghislanzoni3
1Department of Physics, Politecnico di Milano, Milan, Italy.
Abstract:
Anticancer therapy screening in vitro identifies additional treatments and improves clinical outcomes. Systematically, although most tested cells respond to cues with apoptosis, an appreciable portion enters a senescent state, a critical condition potentially driving tumor resistance and relapse. Conventional screening protocols would strongly benefit from prompt identification and monitoring of therapy-induced senescent (TIS) cells in their native form. We combined complementary all-optical, label-free, and quantitative microscopy techniques, based on coherent Raman scattering, multiphoton absorption, and interferometry, to explore the early onset and progression of this phenotype, which has been understudied in unperturbed conditions. We identified TIS manifestations as early as 24 hours following treatment, consisting of substantial mitochondrial rearrangement and increase of volume and dry mass, followed by accumulation of lipid vesicles starting at 72 hours. This work holds the potential to affect anticancer treatment research, by offering a label-free, rapid, and accurate method to identify initial TIS in tumor cells.
Insights
This study introduces a label-free microscopy method to rapidly detect therapy-induced senescent (TIS) cells in cancer research. Early identification of TIS cells can improve anticancer treatments and patient outcomes.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Anticancer therapy screening is crucial for improving clinical outcomes, but conventional methods overlook therapy-induced senescence (TIS).
- Senescent cells can drive tumor resistance and relapse, highlighting the need for their early detection.
- Current protocols lack methods for prompt and accurate identification of TIS cells in their native state.
Purpose of the Study:
- To develop and validate an all-optical, label-free microscopy technique for early detection of therapy-induced senescent cells.
- To monitor the early onset and progression of TIS phenotype in unperturbed cancer cells.
- To provide a rapid and accurate method for identifying initial TIS in tumor cells for improved anticancer research.
Main Methods:
- Utilized complementary all-optical, label-free, and quantitative microscopy techniques.
- Employed coherent Raman scattering, multiphoton absorption, and interferometry for cellular analysis.
- Focused on observing TIS in unperturbed conditions to capture early, subtle changes.
Main Results:
- Identified TIS manifestations as early as 24 hours post-treatment.
- Observed significant mitochondrial rearrangement, increased cell volume, and dry mass in TIS cells.
- Detected accumulation of lipid vesicles starting at 72 hours in TIS cells.
Conclusions:
- The developed label-free microscopy method enables rapid and accurate identification of initial TIS.
- This technique offers a significant advancement for monitoring senescent cells in anticancer therapy research.
- Early detection of TIS can potentially impact the development of more effective anticancer treatments.
