NDLI: Myeloma cells can corrupt senescent mesenchymal stromal cells and impair their anti-tumor activity

Content Provider	PubMed Central
Author	Özcan, Servet Alessio, Nicola Acar, Mustafa Burak Toprak, Güler Burcin, Gönen Zeynep Peluso, Gianfranco Galderisi, Umberto
Copyright Year	2015
Abstract	Senescent cells secrete several molecules that help to prevent the progression of cancer. However, cancer cells can also misuse these secreted elements to survive and grow. Since the molecular and functional bases of these different elements remain poorly understood, we analyzed the effect of senescent mesenchymal stromal cell (MSC) secretome on the biology of ARH-77 myeloma cells. In addition to differentiating in mesodermal derivatives, MSCs have sustained interest among researchers by supporting hematopoiesis, contributing to tissue homeostasis, and modulating inflammatory response, all activities accomplished primarily by the secretion of cytokines and growth factors. Moreover, senescence profoundly affects the composition of MSC secretome. In this study, we induced MSC senescence by oxidative stress, DNA damage, and replicative exhaustion. While the first two are considered to induce acute senescence, extensive proliferation triggers replicative (i.e., chronic) senescence. We cultivated cancer cells in the presence of acute and chronic senescent MSC-conditioned media and evaluated their proliferation, DNA damage, apoptosis, and senescence. Our findings revealed that senescent secretomes induced apoptosis or senescence, if not both, to different extents. This anti-tumor activity became heavily impaired when secretomes were collected from senescent cells previously in contact (i.e., primed) with cancer cells. Our analysis of senescent MSC secretomes with LC-MS/MS followed by Gene Ontology classification further indicated that priming with cancer profoundly affected secretome composition by abrogating the production of pro-senescent and apoptotic factors. We thus showed for the first time that compared with cancer-primed MSCs, naïve senescent MSCs can exert different effects on tumor progression.
Ending Page	39492
Starting Page	39482
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	37
Volume Number	6
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-10-16
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

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