Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1

2016
Authors
Trivanović, Drenka
Jauković, Aleksandra

Krstić, Jelena

Nikolić, Srdjan
Okić-Đorđević, Ivana

Kukolj, Tamara

Obradović, Hristina

Mojsilović, Slavko

Ilić, Vesna

Santibanez, Juan

Bugarski, Diana

Article (Published version)

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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-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-gamma and/or TNF-alpha-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-beta 1(TGF-beta 1) in cytokines-primed hASCs, since inhibition of type... I TGF-beta 1 receptor on MCF-7 cells and neutralization of TGF-beta 1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-gamma and/or TNF-alpha primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-beta 1-Smad3 signalization, with potentially important implications in breast cancer progression.
Keywords:
adipose tissue mesenchymal stem cells / MCF-7 / inflammatory cytokines / EMT / urokinase type-plasminogen activatorSource:
Iubmb Life, 2016, 68, 3, 190-200Publisher:
- Wiley, Hoboken
Funding / projects:
DOI: 10.1002/iub.1473
ISSN: 1521-6543
PubMed: 26805406
WoS: 000373132500003
Scopus: 2-s2.0-84959350888
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Institut za medicinska istraživanjaTY - JOUR AU - Trivanović, Drenka AU - Jauković, Aleksandra AU - Krstić, Jelena AU - Nikolić, Srdjan AU - Okić-Đorđević, Ivana AU - Kukolj, Tamara AU - Obradović, Hristina AU - Mojsilović, Slavko AU - Ilić, Vesna AU - Santibanez, Juan AU - Bugarski, Diana PY - 2016 UR - http://rimi.imi.bg.ac.rs/handle/123456789/726 AB - 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-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-gamma and/or TNF-alpha-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-beta 1(TGF-beta 1) in cytokines-primed hASCs, since inhibition of type I TGF-beta 1 receptor on MCF-7 cells and neutralization of TGF-beta 1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-gamma and/or TNF-alpha primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-beta 1-Smad3 signalization, with potentially important implications in breast cancer progression. PB - Wiley, Hoboken T2 - Iubmb Life T1 - Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1 EP - 200 IS - 3 SP - 190 VL - 68 DO - 10.1002/iub.1473 ER -
@article{ author = "Trivanović, Drenka and Jauković, Aleksandra and Krstić, Jelena and Nikolić, Srdjan and Okić-Đorđević, Ivana and Kukolj, Tamara and Obradović, Hristina and Mojsilović, Slavko and Ilić, Vesna and Santibanez, Juan and Bugarski, Diana", year = "2016", 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-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-gamma and/or TNF-alpha-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-beta 1(TGF-beta 1) in cytokines-primed hASCs, since inhibition of type I TGF-beta 1 receptor on MCF-7 cells and neutralization of TGF-beta 1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFN-gamma and/or TNF-alpha primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-beta 1-Smad3 signalization, with potentially important implications in breast cancer progression.", publisher = "Wiley, Hoboken", journal = "Iubmb Life", title = "Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1", pages = "200-190", number = "3", volume = "68", doi = "10.1002/iub.1473" }
Trivanović, D., Jauković, A., Krstić, J., Nikolić, S., Okić-Đorđević, I., Kukolj, T., Obradović, H., Mojsilović, S., Ilić, V., Santibanez, J.,& Bugarski, D.. (2016). Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1. in Iubmb Life Wiley, Hoboken., 68(3), 190-200. https://doi.org/10.1002/iub.1473 conv_3727
Trivanović D, Jauković A, Krstić J, Nikolić S, Okić-Đorđević I, Kukolj T, Obradović H, Mojsilović S, Ilić V, Santibanez J, Bugarski D. Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1. in Iubmb Life. 2016;68(3):190-200. doi:10.1002/iub.1473 conv_3727 .
Trivanović, Drenka, Jauković, Aleksandra, Krstić, Jelena, Nikolić, Srdjan, Okić-Đorđević, Ivana, Kukolj, Tamara, Obradović, Hristina, Mojsilović, Slavko, Ilić, Vesna, Santibanez, Juan, Bugarski, Diana, "Inflammatory Cytokines Prime Adipose Tissue Mesenchymal Stem Cells to Enhance Malignancy of MCF-7 Breast Cancer Cells via Transforming Growth Factor-beta 1" in Iubmb Life, 68, no. 3 (2016):190-200, https://doi.org/10.1002/iub.1473 ., conv_3727 .