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Article

Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment

by
Hui-Kung Ting
1,
Chin-Li Chen
1,
En Meng
1,2,
Juin-Hong Cherng
3,4,
Shu-Jen Chang
5,
Chien-Chang Kao
1,
Ming-Hsin Yang
1,
Fang-Shiuan Leung
6 and
Sheng-Tang Wu
1,*
1
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
2
Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan
3
Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan
4
Department of Gerontological Health Care, National Taipei University of Nursing and Health Sciences, Taipei 112, Taiwan
5
Laboratory of Adult Stem Cell and Tissue Regeneration, National Defense Medical Center, Taipei 114, Taiwan
6
College of Biological Science, University of California-Davis, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(8), 3987; https://doi.org/10.3390/ijms22083987
Submission received: 18 March 2021 / Revised: 7 April 2021 / Accepted: 9 April 2021 / Published: 13 April 2021
(This article belongs to the Special Issue Adipose Stem Cells 3.0)
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Abstract

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.
Keywords: adipose-derived stem cells; immunomodulatory; tumor necrosis factor-α; tumorigenicity; bladder cancer; inflammatory microenvironment adipose-derived stem cells; immunomodulatory; tumor necrosis factor-α; tumorigenicity; bladder cancer; inflammatory microenvironment

Share and Cite

MDPI and ACS Style

Ting, H.-K.; Chen, C.-L.; Meng, E.; Cherng, J.-H.; Chang, S.-J.; Kao, C.-C.; Yang, M.-H.; Leung, F.-S.; Wu, S.-T. Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment. Int. J. Mol. Sci. 2021, 22, 3987. https://doi.org/10.3390/ijms22083987

AMA Style

Ting H-K, Chen C-L, Meng E, Cherng J-H, Chang S-J, Kao C-C, Yang M-H, Leung F-S, Wu S-T. Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment. International Journal of Molecular Sciences. 2021; 22(8):3987. https://doi.org/10.3390/ijms22083987

Chicago/Turabian Style

Ting, Hui-Kung, Chin-Li Chen, En Meng, Juin-Hong Cherng, Shu-Jen Chang, Chien-Chang Kao, Ming-Hsin Yang, Fang-Shiuan Leung, and Sheng-Tang Wu. 2021. "Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment" International Journal of Molecular Sciences 22, no. 8: 3987. https://doi.org/10.3390/ijms22083987

APA Style

Ting, H.-K., Chen, C.-L., Meng, E., Cherng, J.-H., Chang, S.-J., Kao, C.-C., Yang, M.-H., Leung, F.-S., & Wu, S.-T. (2021). Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment. International Journal of Molecular Sciences, 22(8), 3987. https://doi.org/10.3390/ijms22083987

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