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

Lindoso RS, Collino F, Camussi G - Oncotarget (2015)

Bottom Line: 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).Moreover, EV-stimulated MSCs enhanced migration of renal tumor cells and induced vessel-like formation.In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences and Molecular Biotechnology Center University of Torino, Torino, Italy.

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 and vascularization, when co-injected with renal tumor cells. In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth.

No MeSH data available.


Related in: MedlinePlus

Uptake of CSC-EVs by MSCsCSC-EVs stained with Vybrant Dil (in red) were incubated for 6, 24, 48 and 72 hours with MSCs. Cytoplasm staining of MSCs was obtained by using Syto-RNA dye (in green). The nuclei of MSCs were stained with DAPI (in blue). The different times of incubation are identified. Images were obtained with original magnification × 60. Images are representative of three different experiments.
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Figure 1: Uptake of CSC-EVs by MSCsCSC-EVs stained with Vybrant Dil (in red) were incubated for 6, 24, 48 and 72 hours with MSCs. Cytoplasm staining of MSCs was obtained by using Syto-RNA dye (in green). The nuclei of MSCs were stained with DAPI (in blue). The different times of incubation are identified. Images were obtained with original magnification × 60. Images are representative of three different experiments.

Mentions: CSC-EV uptake by MSCs was assessed by maintaining cells incubated with stained CSC-EVs for different periods of time. As shown in Fig. 1, CSC-EVs (in red) were detectable within MSCs already at 6 hours to increase thereafter up to 72 h. Experiments were performed in order to asses population doubling time on MSCs stimulated with CSC-EVs and unstimulated MSCs. No change in population doubling time was observed between the two groups (data not shown).


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

Lindoso RS, Collino F, Camussi G - Oncotarget (2015)

Uptake of CSC-EVs by MSCsCSC-EVs stained with Vybrant Dil (in red) were incubated for 6, 24, 48 and 72 hours with MSCs. Cytoplasm staining of MSCs was obtained by using Syto-RNA dye (in green). The nuclei of MSCs were stained with DAPI (in blue). The different times of incubation are identified. Images were obtained with original magnification × 60. Images are representative of three different experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480728&req=5

Figure 1: Uptake of CSC-EVs by MSCsCSC-EVs stained with Vybrant Dil (in red) were incubated for 6, 24, 48 and 72 hours with MSCs. Cytoplasm staining of MSCs was obtained by using Syto-RNA dye (in green). The nuclei of MSCs were stained with DAPI (in blue). The different times of incubation are identified. Images were obtained with original magnification × 60. Images are representative of three different experiments.
Mentions: CSC-EV uptake by MSCs was assessed by maintaining cells incubated with stained CSC-EVs for different periods of time. As shown in Fig. 1, CSC-EVs (in red) were detectable within MSCs already at 6 hours to increase thereafter up to 72 h. Experiments were performed in order to asses population doubling time on MSCs stimulated with CSC-EVs and unstimulated MSCs. No change in population doubling time was observed between the two groups (data not shown).

Bottom Line: 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).Moreover, EV-stimulated MSCs enhanced migration of renal tumor cells and induced vessel-like formation.In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences and Molecular Biotechnology Center University of Torino, Torino, Italy.

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 and vascularization, when co-injected with renal tumor cells. In conclusion, CSC-derived EVs induced phenotypical changes in MSCs that are associated with tumor growth.

No MeSH data available.


Related in: MedlinePlus