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Research Paper|Volume 8, Issue 7|pp 1316—1327

Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses

Servet Özcan1,2, Nicola Alessio4, Mustafa B. B. Acar1,2, Eda Mert1,2, Fatih Omerli1,2, Gianfranco Peluso5, Umberto Galderisi1,3,4
  • 1Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
  • 2Department of Biology, Faculty of Sciences, Erciyes University, Kayseri, Turkey
  • 3Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA
  • 4Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy
  • 5Institute of Bioscience and Bioresources, CNR, Naples, Italy
Received: March 16, 2016Accepted: May 28, 2016Published: June 9, 2016
https://doi.org/10.18632/aging.100971

Copyright: © 2016 Özcan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions, such as sensitizing surrounding cells to senesce; immunomodulation; impairing or fostering cancer growth; and promoting tissue development. Identifying secreted factors that achieve such tasks is a challenging issue since the profile of secreted proteins depends on genotoxic stress and cell type. Currently, researchers are trying to identify common markers for SASP. The present investigation compared the secretome composition of five different senescent phenotypes in two different cell types: bone marrow and adipose mesenchymal stromal cells (MSC). We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation, and replicative exhaustion. We took advantage of LC-MS/MS proteome identification and subsequent gene ontology (GO) evaluation to perform an unbiased analysis (hypothesis free manner) of senescent secretomes. GO analysis allowed us to distribute SASP components into four classes: extracellular matrix/cytoskeleton/cell junctions; metabolic processes; ox-redox factors; and regulators of gene expression.

We used Ingenuity Pathway Analysis (IPA) to determine common pathways among the different senescent phenotypes. This investigation, along with identification of eleven proteins that were exclusively expressed in all the analyzed senescent phenotypes, permitted the identification of three key signaling paths: MMP2 - TIMP2; IGFBP3 - PAI-1; and Peroxiredoxin 6 - ERP46 - PARK7 - Cathepsin D - Major vault protein. We suggest that these paths could be involved in the paracrine circuit that induces senescence in neighboring cells and may confer apoptosis resistance to senescent cells.