Next Article in Journal
Connecting Cancer Pathways to Tumor Engines: A Stratification Tool for Colorectal Cancer Combining Human In Vitro Tissue Models with Boolean In Silico Models
Previous Article in Journal
Allometric Scaling Approaches for Predicting Human Pharmacokinetic of a Locked Nucleic Acid Oligonucleotide Targeting Cancer-Associated miR-221
Open AccessArticle

Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer

by Jyun-Yuan Huang 1,2, Yen-Yun Wang 1,2,3,4, Steven Lo 5, Ling-Ming Tseng 6, Dar-Ren Chen 7, Yi-Chia Wu 8,9,10,11, Ming-Feng Hou 12 and Shyng-Shiou F. Yuan 1,2,3,13,14,15,16,*
1
Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
5
College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
6
Comprehensive Breast Health Center, Department of Surgery, Taipei-Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
7
Breast Cancer Center, Changhua Christian Hospital, Changhua 500, Taiwan
8
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linko, Taoyuan 333, Taiwan
9
Research Center of Regenerative Medicine and Cell Therapy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
10
Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
11
Center of Teaching and Research, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan
12
Division of Breast Surgery, Department of Surgery, Center for Cancer Research, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung 807, Taiwan
13
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
14
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
15
Department of Biological Science and Technology, College of Biological Science and Technology, National ChiaoTung University, Hsinchu 300, Taiwan
16
Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University, Hsinchu 300, Taiwan
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 29; https://doi.org/10.3390/cancers12010029
Received: 19 October 2019 / Revised: 16 December 2019 / Accepted: 18 December 2019 / Published: 20 December 2019
(This article belongs to the Special Issue How Does Obesity Cause Cancer? )
Adipose-derived stem cells (ADSCs) have been implicated in tumor growth and metastasis in breast cancer. ADSCs exhibit tumor tropism, and are of increasing clinical relevance due to the autologous fat grafting for breast reconstruction. Although we have previously shown that a high level of the adipocytokine visfatin in human breast cancer tissues correlated with tumor progression mediated by cAbl and STAT3, the effects of visfatin in the tumor microenvironment are unclear. To understand how visfatin modulates breast cancer within the tumor-stromal environment, we examined determinants of breast cancer progression using a visfatin-primed ADSCs-tumor co-culture model. ADSCs were isolated from tumor-free adipose tissue adjacent to breast tumors. ADSCs were treated with or without visfatin for 48 h and then collected for co-culture with breast cancer cell line MDA-MB-231 for 72 h in a transwell system. We found that the MDA-MB-231 cells co-cultured with visfatin-treated ADSCs (vADSCs) had higher levels of cell viability, anchorage independent growth, migration, invasion, and tumorsphere formation than that co-cultured with untreated ADSCs (uADSCs). Growth differentiation factor 15 (GDF15) upregulation was found in the co-culture conditioned medium, with GDF15 neutralizing antibody blocking the promoting effect on MDA-MB-231 in co-culture. In addition, a GDF15-induced AKT pathway was found in MDA-MB-231 and treatment with PI3K/AKT inhibitor also reversed the promoting effect. In an orthotopic xenograft mouse model, MDA-MB-231 co-injected with vADSCs formed a larger tumor mass than with uADSCs. Positive correlations were noted between visfatin, GDF15, and phosphor-AKT expressions in human breast cancer specimens. In conclusion, visfatin activated GDF15-AKT pathway mediated via ADSCs to facilitate breast cancer progression. View Full-Text
Keywords: breast cancer; visfatin; adipose-derived stem cells (ADSCs); GDF15 breast cancer; visfatin; adipose-derived stem cells (ADSCs); GDF15
Show Figures

Figure 1

MDPI and ACS Style

Huang, J.-Y.; Wang, Y.-Y.; Lo, S.; Tseng, L.-M.; Chen, D.-R.; Wu, Y.-C.; Hou, M.-F.; Yuan, S.-S.F. Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer. Cancers 2020, 12, 29.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop