A Human-Like Senescence-Associated Secretory Phenotype Is Conserved in Mouse Cells Dependent on Physiological Oxygen

• DOI: 10.1371/journal.pone.0009188
• Publication Date: 2010-02-11T23:21:36Z
• Authors: Jean-Philippe Coppé; Christopher K. Patil; Francis Rodier; Ana Krtolica; Christian M. Beau...; Simona Parrinello; J. Graeme Hodgson; Koei Chin; Pierre-Yves Desprez; Judith Campisi
• Keywords: Senescence

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 behavior neighboring cells. We show here "senescent" mouse fibroblasts, arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express human-like SASP, differ from similarly cultured human respects. However, when physiological (3%) oxygen induced senesce by radiation, more closely resemble cells, including expression robust SASP. describe two new aspects SASPs. First, both species upregulated several matrix metalloproteinases, comprise conserved genomic cluster. Second, for species, ability promote premalignant epithelial was due primarily SASP factor CXCL-1/KC/GRO-α. Further, fibroblasts made senescent 3%, but 20%, promoted tumorigenesis xenographs. Our findings underscore critical mouse-human differences sensitivity, identify use model cellular senescence, reveal novel features