title: Inflammatory cytokines prime adipose tissue mesenchymal stem cells to enhance malignancy of MCF-7 breast cancer cells via transforming growth factor-β1.
abstract: Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs-affected tumor development is not understood. We found that interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-γ and/or TNF-α-primed hASCs produced conditioned media (CM) which induced epithelial to mesenchymal transition (EMT) of MCF-7 cells by reducing E-Cadherin and increasing Vimentin expression. Induced EMT was accompanied by increased invasion, migration, and urokinase type-plasminogen activator (uPA) expression in MCF-7 cells. These effects were mediated by increased expression of transforming growth factor-β1(TGF-β1) in cytokines-primed hASCs, since inhibition of type I TGF-β1 receptor on MCF-7 cells and neutralization of TGF-β1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-γ and/or TNF-α primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-β1-Smad3 signalization, with potentially important implications in breast cancer progression.
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Drenka
authors.initials: D
authors.lastname: Trivanović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jauković
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Krstić
authors.affiliation: Institute of Oncology and Radiology, Belgrade, Serbia.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Nikolić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Okić Djordjević
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kukolj
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Hristina
authors.initials: H
authors.lastname: Obradović
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Laboratory for Immunology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilić
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Santibanez
authors.affiliation: Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Diana
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
chemical_list: C508960:TGFB1 protein, human; C439524:TNF protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014568:Urokinase-Type Plasminogen Activator
keywords: EMT; MCF-7; adipose tissue mesenchymal stem cells; inflammatory cytokines; urokinase type-plasminogen activator