Dynamic bioinspired coculture model for probing ER+ breast cancer dormancy in the bone marrow niche

Pradhan, Lina
Moore, DeVonte
Ovadia, Elisa M.
Swedzinski, Samantha L.
Cossette, Travis
Sikes, Robert A.
van Golen, Kenneth
Kloxin, April M.
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Science Advances
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.
This article was originally published in Science Advances. The version of record is available at: https://doi.org/10.1126/sciadv.ade3186
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