Cellular senescence suppresses cancer by arresting cell proliferation, 
essentially permanently, in response to oncogenic stimuli, including genotoxic 
stress. We modified the use of antibody arrays to provide a quantitative 
assessment of factors secreted by senescent cells. We show that human cells 
induced to senesce by genotoxic stress secrete myriad factors associated with 
inflammation and malignancy. This senescence-associated secretory phenotype 
(SASP) developed slowly over several days and only after DNA damage of 
sufficient magnitude to induce senescence. Remarkably similar SASPs developed in 
normal fibroblasts, normal epithelial cells, and epithelial tumor cells after 
genotoxic stress in culture, and in epithelial tumor cells in vivo after 
treatment of prostate cancer patients with DNA-damaging chemotherapy. In 
cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme 
transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism 
that depended largely on the SASP factors interleukin (IL)-6 and IL-8. 
Strikingly, two manipulations markedly amplified, and accelerated development 
of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and 
senescence in normal cells, and functional loss of the p53 tumor suppressor 
protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the 
promalignant paracrine activities of the SASPs. Our findings define a central 
feature of genotoxic stress-induced senescence. Moreover, they suggest a 
cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can 
promote, the development of age-related cancer by altering the tissue 
microenvironment.