A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen
Abstract
Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that ‘‘senescent’’ mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-a. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.
- Authors:
-
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Buck Inst. for Age Research, Navato, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
- Univ. of Montreal, QC (Canada). Centre de Recherche du CHU Ste-Justine et De´partement de Pharmacologie
- Univ. of California, San Francisco, CA (United States). Comprehensive Cancer Center. Dept. of Lab. Medicine
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Buck Inst. for Age Research, Navato, CA (United States); California Pacific Medical Center Research Inst., San Francisco, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1627397
- Grant/Contract Number:
- AC03-76SF00098
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 5; Journal Issue: 2; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics
Citation Formats
Coppé, Jean-Philippe, Patil, Christopher K., Rodier, Francis, Krtolica, Ana, Beauséjour, Christian M., Parrinello, Simona, Hodgson, J. Graeme, Chin, Koei, Desprez, Pierre-Yves, Campisi, Judith, and Blagosklonny, Mikhail V. A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen. United States: N. p., 2010.
Web. doi:10.1371/journal.pone.0009188.
Coppé, Jean-Philippe, Patil, Christopher K., Rodier, Francis, Krtolica, Ana, Beauséjour, Christian M., Parrinello, Simona, Hodgson, J. Graeme, Chin, Koei, Desprez, Pierre-Yves, Campisi, Judith, & Blagosklonny, Mikhail V. A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen. United States. https://doi.org/10.1371/journal.pone.0009188
Coppé, Jean-Philippe, Patil, Christopher K., Rodier, Francis, Krtolica, Ana, Beauséjour, Christian M., Parrinello, Simona, Hodgson, J. Graeme, Chin, Koei, Desprez, Pierre-Yves, Campisi, Judith, and Blagosklonny, Mikhail V. Fri .
"A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen". United States. https://doi.org/10.1371/journal.pone.0009188. https://www.osti.gov/servlets/purl/1627397.
@article{osti_1627397,
title = {A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen},
author = {Coppé, Jean-Philippe and Patil, Christopher K. and Rodier, Francis and Krtolica, Ana and Beauséjour, Christian M. and Parrinello, Simona and Hodgson, J. Graeme and Chin, Koei and Desprez, Pierre-Yves and Campisi, Judith and Blagosklonny, Mikhail V.},
abstractNote = {Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that ‘‘senescent’’ mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-a. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.},
doi = {10.1371/journal.pone.0009188},
journal = {PLoS ONE},
number = 2,
volume = 5,
place = {United States},
year = {Fri Feb 12 00:00:00 EST 2010},
month = {Fri Feb 12 00:00:00 EST 2010}
}
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