Dynamic bioinspired coculture model for probing ER+ breast cancer dormancy in the bone marrow niche
| Author(s) | Pradhan, Lina | |
| Author(s) | Moore, DeVonte | |
| Author(s) | Ovadia, Elisa M. | |
| Author(s) | Swedzinski, Samantha L. | |
| Author(s) | Cossette, Travis | |
| Author(s) | Sikes, Robert A. | |
| Author(s) | van Golen, Kenneth | |
| Author(s) | Kloxin, April M. | |
| Date Accessioned | 2023-05-04T13:28:22Z | |
| Date Available | 2023-05-04T13:28:22Z | |
| Publication Date | 2023-03-08 | |
| Description | This article was originally published in Science Advances. The version of record is available at: https://doi.org/10.1126/sciadv.ade3186 | |
| Abstract | Late recurrences of breast cancer are hypothesized to arise from disseminated tumor cells (DTCs) that reactivate after dormancy and occur most frequently with estrogen receptor–positive (ER+) breast cancer cells (BCCs) in bone marrow (BM). Interactions between the BM niche and BCCs are thought to play a pivotal role in recurrence, and relevant model systems are needed for mechanistic insights and improved treatments. We examined dormant DTCs in vivo and observed DTCs near bone lining cells and exhibiting autophagy. To study underlying cell-cell interactions, we established a well-defined, bioinspired dynamic indirect coculture model of ER+ BCCs with BM niche cells, human mesenchymal stem cells (hMSCs) and fetal osteoblasts (hFOBs). hMSCs promoted BCC growth, whereas hFOBs promoted dormancy and autophagy, regulated in part by tumor necrosis factor–α and monocyte chemoattractant protein 1 receptor signaling. This dormancy was reversible by dynamically changing the microenvironment or inhibiting autophagy, presenting further opportunities for mechanistic and targeting studies to prevent late recurrence. | |
| Sponsor | This work was supported by a grant from the Susan G. Komen Foundation (CCR16377327) made possible by funding from American Airlines, as well as an NIH Director’s New Innovator Award (DP2 HL152424-01) for related research. Fellowship support for D.M. was provided in part by the National Institute of General Medical Sciences (NIGMS) of the NIH under award number T32GM133395. Facilities and instrumentation were supported by an Institutional Development Award (IDeA) for a Center of Biomedical Research Excellence (COBRE) from the NIGMS within the NIH (P20GM104316 and P20 GM103446) and by the NSF through the University of Delaware Materials Research Science and Engineering Center (DMR-2011824). | |
| Citation | Lina Pradhan et al. ,Dynamic bioinspired coculture model for probing ER+ breast cancer dormancy in the bone marrow niche.Sci. Adv.9,eade3186(2023).DOI:10.1126/sciadv.ade3186 | |
| ISSN | 2375-2548 | |
| URL | https://udspace.udel.edu/handle/19716/32719 | |
| Language | en_US | |
| Publisher | Science Advances | |
| Keywords | good health and well-being | |
| Title | Dynamic bioinspired coculture model for probing ER+ breast cancer dormancy in the bone marrow niche | |
| Type | Article |
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