Senescent cells as a source of inflammatory factors for tumor progression

Abstract

Cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, therefore constituting a potent tumor suppressive mechanism. Recent studies show that, despite the beneficial effects of cellular senescence, senescent cells can also exert harmful effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescent-associated secretory phenotype (SASP), which entails a striking increase in the secretion of pro-inflammatory cytokines. Here, we summarize our knowledge of the SASP and the impact it has on tissue microenvironments and ability to stimulate tumor progression.

Fig. 1

Stimuli that trigger cellular senescence. DNA damage or mitogenic signals of sufficient magnitude, as well as other stresses, can cause cells to permanently arrest and senesce. Most of these senescence inducers lead to the acquisition of multiple senescence markers (right panel), including the senescence secretory phenotype (SASP factors). PRE pre-senescent, SEN senescent

Fig. 2

Pro-tumorigenic paracrine effects of senescent cells. Senescent stromal fibroblasts can promote various facets of cancer progression (right panel). Pre-neopastic or transformed epithelial cells are shown in dark color; senescent cells cells are represented in dark gray. Pre-senescent and senesent fibroblasts secrete SASP factors that can promote cancer progression and aggressiveness