Senescence-Associated Exosome Release from Human Prostate Cancer Cells
Open accessAbstract
Males of advanced age represent a rapidly growing population at risk for prostate cancer. In the contemporary setting of earlier detection, a majority of prostate carcinomas are still clinically localized and often treated using radiation therapy. Our recent studies have shown that premature cellular senescence, rather than apoptosis, accounts for most of the clonogenic death induced by clinically relevant doses of irradiation in prostate cancer cells. We show here that this treatment-induced senescence was associated with a significantly increased release of exosome-like microvesicles. In premature senescence, this novel secretory phenotype was dependent on the activation of p53. In addition, the release of exosome-like microvesicles also increased during proliferative senescence in normal human diploid fibroblasts. These data support the hypothesis that senescence, initiated either by telomere attrition (e.g., aging) or DNA damage (e.g., radiotherapy), may induce a p53-dependent increase in the biogenesis of exosome-like vesicles. Ultrastructural analysis and RNA interference-mediated knockdown of Tsg101 provided significant evidence that the additional exosomes released by prematurely senescent prostate cancer cells were principally derived from multivesicular endosomes. Moreover, these exosomes were enriched in B7-H3 protein, a recently identified diagnostic marker for prostate cancer, and an abundance of what has recently been termed "exosomal shuttle RNA." Our findings are consistent with the proposal that exosomes can transfer cargos, with both immunoregulatory potential and genetic information, between cells through a novel mechanism that may be recruited to increase exosome release during accelerated and replicative cellular senescence.
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Some senescent cells secrete exosomes, which may have a tumour promoter function.
“In particular, some senescent cells secrete exosomes [56] (small “packages” containing a variety of proteins and mRNA) and these may have a tumour promoter function [55].”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [56]
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- Authors
- Lehmann, B. D., Paine, M. S., Brooks, A. M., McCubrey, J. A., Renegar, R. H., Wang, R., & Terrian, D. M.
- Affiliations
- 1Anatomy and Cell Biology and Departments of
- East Carolina University (US)
- Venue
- Cancer Research
- Published
- 2008-09-30
- Volume
- 68
- Issue
- 19
- Pages
- 7864-7871
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3845029
- OpenAlex
- W2116842394
- Cited by
- 464
- References
- 34
- Citations by year
- 2026: 10 · 2025: 27 · 2024: 32 · 2023: 27 · 2022: 52 · 2021: 46 · 2020: 61 · 2019: 37 · 2018: 34 · 2017: 28 · 2016: 12 · 2015: 19 · 2014: 20 · 2013: 13 · 2012: 16
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA098195, R01CA051025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- cellular senescence, exosome secretion, prostate cancer, radiation-induced senescence, p53, microvesicles, TSG101, multivesicular endosomes, B7-H3, intercellular communication, telomere shortening, DNA damage
- MeSH terms
- Carcinoma, Exocytosis, Humans, Male, Prostatic Neoplasms, Endosomes, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Cellular Senescence, Secretory Vesicles
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