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

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2016
723.pdf (1.064Mb)
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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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.

Keywords:
adipose tissue mesenchymal stem cells / MCF-7 / inflammatory cytokines / EMT / urokinase type-plasminogen activator
Source:
Iubmb Life, 2016, 68, 3, 190-200
Publisher:
  • Wiley, Hoboken
Funding / projects:
  • Regenerative and modulatory potential of adult stem cells (RS-175062)

DOI: 10.1002/iub.1473

ISSN: 1521-6543

PubMed: 26805406

WoS: 000373132500003

Scopus: 2-s2.0-84959350888
[ Google Scholar ]
34
27
URI
http://rimi.imi.bg.ac.rs/handle/123456789/726
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - 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 .

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