ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model

Wang, Y.-Y., Hung, A. C., Wu, Y.-C., Lo, S. , Chen, H.-D., Chen, Y.-K., Hsieh, Y.-C., Hu, S. C.‐S., Hou, M.-F. and Yuan, S.-S. F. (2022) ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model. Scientific Reports, 12, 15437. (doi: 10.1038/s41598-022-19290-6) (PMID:36104403) (PMCID:PMC9475041)

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Abstract

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.

Item Type:Articles
Additional Information:Funding: This work was supported by grants from the Ministry of Science and Technology (MOST110-2314-B-037-129, MOST110-2314-B-037-084) and Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) from the Featured Areas Research Center Program within the framework of Higher Education Sprout Project by the Ministry of Education, Taiwan. This work was also supported by grants from Kaohsiung Medical University Hospital (KMUH106-6R83, KMUH107-7R36, KMUH108-8R42, KMUH109-9R42, KMUH-DK(A)110001) and Kaohsiung Medical University (KMU-DK108005, KMU-TC108A04-0, KMU-TC108A04-1), Taiwan.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lo, Professor Steven
Authors: Wang, Y.-Y., Hung, A. C., Wu, Y.-C., Lo, S., Chen, H.-D., Chen, Y.-K., Hsieh, Y.-C., Hu, S. C.‐S., Hou, M.-F., and Yuan, S.-S. F.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:14 September 2022
Copyright Holders:Copyright © The Author(s) 2022
First Published:First published in Scientific Reports 12: 15437
Publisher Policy:Reproduced under a Creative Commons License

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