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Updated: Jun 7, 2026
09:18
A Sensitive Method to Quantify Senescent Cancer Cells
Published on: August 2, 2013
Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor
Jean-Philippe Coppé1, Christopher K Patil, Francis Rodier
1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Plos Biology
|December 5, 2008
Summary
Cellular senescence, a cancer-suppressing mechanism, releases factors that promote malignancy. Manipulating oncogenic RAS or p53 alters this senescence-associated secretory phenotype (SASP), impacting cancer development.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Cellular senescence permanently arrests proliferation in response to oncogenic stimuli.
- Senescence-associated secretory phenotype (SASP) involves factors secreted by senescent cells.
- Understanding SASP's role in cancer is crucial.
Purpose of the Study:
- To quantitatively assess SASP factors secreted by senescent cells.
- To investigate the impact of genotoxic stress on SASP.
- To explore how oncogenic RAS and p53 influence SASP and malignancy.
Main Methods:
- Modified antibody arrays for quantitative SASP assessment.
- Induced cellular senescence via genotoxic stress in various cell types (fibroblasts, epithelial cells, tumor cells).
- Analyzed SASP in cultured cells and in vivo in prostate cancer patients undergoing chemotherapy.
Main Results:
- Genotoxic stress induced senescent cells to secrete numerous inflammation and malignancy-associated factors (SASP).
- SASP developed slowly over days post-DNA damage and was similar across cell types and in vivo.
- SASP promoted epithelial-mesenchyme transition and invasiveness in premalignant cells via IL-6 and IL-8.
- Oncogenic RAS expression and p53 loss amplified and accelerated SASP, exacerbating its pro-malignant effects.
Conclusions:
- Genotoxic stress-induced senescence has a central feature involving SASP.
- SASP can promote malignancy through paracrine mechanisms.
- p53 restrains, while oncogenic RAS promotes, age-related cancer via SASP-mediated microenvironment alterations.
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