title: Senescence and cancer: An evolving inflammatory paradox.
abstract: The senescent phenotype was first described in 1961 as a phenomenon characterized by the cessation of cellular division. After years of debate as to whether it represented a tissue culture artifact or an important biological process, it is now appreciated that senescence plays an important role in tumorigenesis. Further, senescence is integral to normal biological processes such as embryogenesis and the maintenance of tissue homeostasis. Now with defined roles in development, wound healing, tumor promotion and tumor suppression, it is not surprising that attention has turned to refining our understanding of the mechanisms behind, and consequences of, the induction of senescence. One emerging role for senescence lies in the ability of senescence to orchestrate an inflammatory response: factors secreted by senescent cells have been identified in multiple contexts to modulate various aspects of the immune response. As with many of the previously described roles for senescence, the type of inflammation established by the senescence phenotype is varied and dependent on context. In this review, we discuss the current state of the field with a focus on the paradoxical outcomes of the senescence-induced inflammatory responses in the context of cancer. A more complete understanding of senescence and an appreciation for its complexities will be important for eventual development of senescence-targeted therapies.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Ruhland
authors.affiliation: Department of Cell, Developmental & Cancer Biology, and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address: coussenl@ohsu.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO, USA; Department of Cell Biology and Physiology, ICCE Institute, Washington University School of Medicine, Saint Louis, MO, USA; Department of Medicine, ICCE Institute, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address: sheila.stewart@wustl.edu.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D009369:Neoplasms / Q000473:pathology*
keywords: Cancer; Immune cell; Inflammation; Senescence