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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

dc.contributor.authorBayo J.
dc.contributor.authorReal A.
dc.contributor.authorFiore E.J.
dc.contributor.authorMalvicini M.
dc.contributor.authorSganga L.
dc.contributor.authorBolontrade M.
dc.contributor.authorAndriani O.
dc.contributor.authorBizama C.
dc.contributor.authorFresno C.
dc.contributor.authorPodhajcer O.
dc.contributor.authorFernandez E.
dc.contributor.authorGidekel M.
dc.contributor.authorMazzolini G.D.
dc.contributor.authorGarcía M.G.
dc.date.accessioned2020-09-02T22:13:03Z
dc.date.available2020-09-02T22:13:03Z
dc.date.issued2017
dc.identifier10.18632/oncotarget.10288
dc.identifier.citation8, 46, 80235-80248
dc.identifier.issn19492553
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3713
dc.descriptionNew 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 profile of sMSC showed ~500 genes differentially expressed compared with usMSC, being 46 genes related with cell migration and invasion. sMSC increased fibroblasts 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. Copyright: Bayo et al.
dc.language.isoen
dc.publisherImpact Journals LLC
dc.subjectHuman hepatocellular carcinoma
dc.subjectHuman mesenchymal stromal cells
dc.subjectIL-8
dc.subjectMigration
dc.subjectTumor microenvironment
dc.subjectchemokine receptor CXCR1
dc.subjectchemokine receptor CXCR2
dc.subjectCXCL1-2-3 protein
dc.subjectcytokine
dc.subjectinterleukin 8
dc.subjectmonocyte chemotactic protein 1
dc.subjectunclassified drug
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectArticle
dc.subjectbone marrow cell
dc.subjectcell invasion
dc.subjectcell migration
dc.subjectconditioned medium
dc.subjectcontrolled study
dc.subjectendothelium cell
dc.subjectfibroblast
dc.subjectgene expression
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectin vitro study
dc.subjectliver cell carcinoma
dc.subjectmale
dc.subjectmesenchymal stroma cell
dc.subjectmouse
dc.subjectnonhuman
dc.subjecttumor growth
dc.subjecttumor microenvironment
dc.titleIL-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
dc.typeArticle


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