Artículo
IL-8, GRO and MCP-1 produced by hepatocellular carcinoma microenvironment determine the migratory capacity of human bone marrow-derived mesenchymal stromal cells without affecting tumor aggressiveness
Bayo Fina, Juan Miguel
; Real, Alejandrina; Fiore, Esteban Juan
; Malvicini, Mariana
; Sganga, Leonardo
; Bolontrade, Marcela Fabiana
; Adriani, Oscar; Bizama, Carolina; Fresno Rodríguez, Cristóbal
; Podhajcer, Osvaldo Luis
; Fernandez, Elmer Andres
; Gidekel, Manuel; Mazzolini Rizzo, Guillermo Daniel
; García, Mariana Gabriela
Fecha de publicación:
06/2016
Editorial:
Impact Journals
Revista:
Oncotarget
ISSN:
1949-2553
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
New therapies are needed for advanced hepatocellular carcinoma (HCC) and the use of mesenchymal stromal cells (MSCs) carrying therapeutic genes is a promising strategy. HCC produce cytokines recruiting MSCs to the tumor milieu and modifying its biological properties. Our aim was to study changes generated on human MSCs exposed to conditioned media (CM) derived from human HCC fresh samples and xenografts. All CM shared similar cytokines expression pattern including CXCL1-2-3/GRO, CCL2/MCP- 1 and CXCL8/IL-8 being the latter with the highest concentration. Neutralizing and knockdown experiments of CCL2/MCP-1, CXCL8/IL-8, CXCR1 and CXCR2 reduced in vitro MSC migration of ≥20%. Simultaneous CXCR1 and CXCR2 neutralization resulted in 50% of MSC migration inhibition. MSC stimulated with CM (sMSC) from HuH7 or HC-PT-5 showed a 2-fold increase of migration towards the CM compared with unstimulated MSC (usMSC). Gene expression profle of sMSC showed ~500 genes differentially expressed compared with usMSC, being 46 genes related with cell migration and invasion. sMSC increased fbroblasts and endothelial cells chemotaxis. Finally, sMSC with HuH7 CM and then inoculated in HCC tumor bearing-mice did not modify tumor growth. In this work we characterized factors produced by HCC responsible for the changes in MSC chemotactic capacity with would have an impact on therapeutic use of MSCs for human HCC
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Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IIMT)
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA TRASLACIONAL
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA TRASLACIONAL
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Bayo Fina, Juan Miguel; Real, Alejandrina; Fiore, Esteban Juan; Malvicini, Mariana; Sganga, Leonardo; et al.; IL-8, GRO and MCP-1 produced by hepatocellular carcinoma microenvironment determine the migratory capacity of human bone marrow-derived mesenchymal stromal cells without affecting tumor aggressiveness; Impact Journals; Oncotarget; 8; 46; 6-2016; 80235-80248
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