title: Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro.
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. Graphical Abstract 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.
authors.affiliation: 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.
authors.forename: Isabele C
authors.initials: IC
authors.lastname: Iser
authors.affiliation: 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.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Ceschini
authors.affiliation: Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Giovana R
authors.initials: GR
authors.lastname: Onzi
authors.affiliation: 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.
authors.forename: Ana Paula S
authors.initials: AP
authors.lastname: Bertoni
authors.affiliation: Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.affiliation: 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. mwink@ufcspa.edu.br.
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Wink
mesh_terms: D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005910:Glioma / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000199:Actins; D015415:Biomarkers; D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D007770:L-Lactate Dehydrogenase
keywords: Adipose-derived stem cell; C6 glioma cell; Conditioned medium; Epithelial-mesenchymal transition