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Assessing Functional Roles of the Senescence-Associated Secretory Phenotype (SASP)

  • Nicolas Malaquin
  • Véronique Tu
  • Francis Rodier
Part of the Methods in Molecular Biology book series (MIMB, volume 1896)

Abstract

Cellular senescence is linked to many normal biological processes, including tumor suppression, development, and wound healing, but it is also associated with age-related pathologies such as cancer progression. Numerous functions of senescent cells depend on their ability to secrete bioactive molecules, a characteristic termed the senescence-associated secretory phenotype (SASP). Although the SASP is generally described as proinflammatory, its true microenvironmental impact and composition may vary according to cell types (i.e., fibroblasts/epithelial, normal/cancerous) and senescence-triggering stimuli (i.e., replicative senescence, DNA damage-induced senescence, oncogene-induced senescence). The SASP reinforces autocrine cell-autonomous functions such as the senescence-associated proliferation arrest, but also mediates potent paracrine, non-cell-autonomous effects. In a paracrine manner, senescent cells influence the remodeling of surrounding tissues and the biology of adjacent cells, including modulation of proliferation and migration/invasion, reinforcement/induction of peripheral senescence, and immune cell activity or recruitment. Overall, the complexity of the context-dependent SASP composition and varied microenvironmental impact demonstrate the importance of properly assessing SASP functions directly on target cells. In this chapter, we focus on experimental approaches to evaluate the impact of SASP on the proliferation and migration/invasion capacities of target cancer cells. These techniques, with combined supplemental notes, will facilitate the assessment of novel functions of senescent cells on their microenvironment, and can be easily adapted beyond the use of the presented SASP-cancer scenario.

Key words

Migration/invasion assay Proliferation assay Senescence Secretory phenotype Secretome Cell transformation Microenvironment 

Notes

Acknowledgments

We thank all laboratory members for valuable comments and discussions, and Jacqueline Chung for manuscript editing. FR is supported by the Institut du cancer de Montréal and by grants from the Canadian Institute for Health Research (MOP114962), the Terry Fox Research Institute (1030) and by a Fonds de recherche du Québec - Santé (FRQS) junior I-II career awards (22624). NM is supported by a MITACS fellowship. VT has received scholarships from Université de Montréal’s Faculté de médecine and Molecular Biology programs.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nicolas Malaquin
    • 1
  • Véronique Tu
    • 1
  • Francis Rodier
    • 1
    • 2
  1. 1.Centre de Recherche du CHUM (CRCHUM) and Institut du Cancer de MontréalMontrealCanada
  2. 2.Département de Radiologie, Radio-Oncologie et Médecine NucléaireUniversité de MontréalMontrealCanada

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