Extracellular vesicles derived from renal cancer stem cells induce a pro-tumorigenic phenotype in mesenchymal stromal cells

Oncotarget
Rafael Soares LindosoGiovanni Camussi

Abstract

Renal carcinomas have been shown to contain a population of cancer stem cells (CSCs) that present self-renewing capacity and support tumor growth and metastasis. CSCs were shown to secrete large amount of extracellular vesicles (EVs) that can transfer several molecules (proteins, lipids and nucleic acids) and induce epigenetic changes in target cells. Mesenchymal Stromal Cells (MSCs) are susceptible to tumor signalling and can be recruited to tumor regions. The precise role of MSCs in tumor development is still under debate since both pro- and anti-tumorigenic effects have been reported. In this study we analysed the participation of renal CSC-derived EVs in the interaction between tumor and MSCs. We found that CSC-derived EVs promoted persistent phenotypical changes in MSCs characterized by an increased expression of genes associated with cell migration (CXCR4, CXCR7), matrix remodeling (COL4A3), angiogenesis and tumor growth (IL-8, Osteopontin and Myeloperoxidase). EV-stimulated MSCs exhibited in vitro an enhancement of migration toward the tumor conditioned medium. Moreover, EV-stimulated MSCs enhanced migration of renal tumor cells and induced vessel-like formation. In vivo, EV-stimulated MSCs supported tumor development an...Continue Reading

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Citations

Mar 21, 2017·Clinical & Experimental Metastasis·Magdalena SurmanMałgorzata Przybyło
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Methods Mentioned

BETA
light microscopy
FCS
FACS
confocal microscopy

Software Mentioned

Quantity One® Analysis
GraphPad Prism

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