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Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro

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Abstract

Mesenchymal stem cells (MSCs) have recently been described to home to brain tumors and to integrate into the tumor-associated stroma. Understanding the communication between cancer cells and MSCs has become fundamental to determine whether MSC-tumor interactions should be exploited as a vehicle for therapeutic agents or considered a target for intervention. Therefore, we investigated whether conditioned medium from adipose-derived stem cells (ADSCs-CM) modulate glioma tumor cells by analyzing several cell biology processes in vitro. C6 rat glioma cells were treated with ADSCs-CM, and cell proliferation, cell cycle, cell viability, cell morphology, adhesion, migration, and expression of epithelial-mesenchymal transition (EMT)-related surface markers were analyzed. ADSCs-CM did not alter cell viability, cell cycle, and growth rate of C6 glioma cells but increased their migratory capacity. Moreover, C6 cells treated with ADSC-CM showed reduced adhesion and underwent changes in cell morphology. Up-regulation of EMT-associated markers (vimentin, MMP2, and NRAS) was also observed following treatment with ADSC-CM. Our findings demonstrate that the paracrine factors released by ADSCs are able to modulate glioma cell biology. Therefore, ADSC-tumor cell interactions in a tumor microenvironment must be considered in the design of clinical application of stem cell therapy.

Factors released by adipose-derived stem cells (ADSCs) may modulate the biology of C6 glioma cells. When C6 cells are exposed to a conditioned medium from adipose-derived stem cells (ADSCs-CM), some of these cells can undergo an EMT-like process and trans-differentiate into cells with a more mesenchymal phenotype, characterized by enhanced expression of EMT-related surface markers, reduced cell adhesion capacity, increased migratory capacity, as well as changes in cell and nuclei morphology.

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Acknowledgments

The authors would like to thank Marília Remuzzi Zandoná (Laboratório de Análises Clínicas, UFCSPA) for the excellent technical assistance with LDH analysis. This work was supported by the Conselho de Desenvolvimento Científico e Tecnológico (CNPq-Brasil) (Edital Universal 475882/2012-1 and Novas Terapias Portadoras de Futuro 457394/2013-7); Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (Edital Pronem 11/2072-2); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brasil) (Edital Probitec 004/2012). I.C. Iser and A.P.S. Bertoni are recipients of CAPES PhD and PNPD-Pos-doc fellowship, respectively. M.R. Wink and G. Lenz are recipients of CNPq research productivity fellow.

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Authors and Affiliations

  1. Departamento de Ciências Básicas da Saúde e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Rua Sarmento Leite, 245, CEP 90050-170, Porto Alegre, RS, Brazil

    Isabele C. Iser, Stefanie M. Ceschini, Ana Paula S. Bertoni & Márcia R. Wink

  2. Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil

    Giovana R. Onzi & Guido Lenz

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  1. Isabele C. Iser
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  2. Stefanie M. Ceschini
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  3. Giovana R. Onzi
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  4. Ana Paula S. Bertoni
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  5. Guido Lenz
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  6. Márcia R. Wink
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Correspondence to Márcia R. Wink.

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Fig. 1

ADSC characterization. The differentiation of ADSCs is shown in light microscopy. A. Immunophenotyping analysis of surface markers expression in ADCSs. Flow cytometry histograms show the expression (bold line) of selected molecules (CD90, CD29, CD11b and CD45) by ADSC populations in comparison with controls. B. ADSCs differentiated into adipocyte-like cells, which was stained by Oil Red O, the triglyceride specific dye. C. Cells differentiated into osteoblasts showing the bone matrix stained by Alizarin Red, the calcium-specific marker. D. Cells differentiated into chondrocytes showing the proteoglycan rich matrix stained by Alcian blue. B and D: Magnification, X 400. C: Magnifications, X 200 (GIF 595 kb)

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Iser, I.C., Ceschini, S.M., Onzi, G.R. et al. Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro. Mol Neurobiol 53, 7184–7199 (2016). https://doi.org/10.1007/s12035-015-9585-4

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  • DOI: https://doi.org/10.1007/s12035-015-9585-4

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