Breast cancer dormancy is associated with a 4NG1 state and not senescence

乳腺癌休眠与 4NG1 状态有关,而非衰老

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作者:Chloé Prunier, Ania Alay, Michiel van Dijk, Kelly L Ammerlaan, Sharon van Gelderen, Dieuwke L Marvin, Amina Teunisse, Roderick C Slieker, Karoly Szuhai, A G Jochemsen, Xavier Solé, Peter Ten Dijke, Laila Ritsma

Abstract

Reactivation of dormant cancer cells can lead to cancer relapse, metastasis, and patient death. Dormancy is a nonproliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and ZR-75-1, and proliferative D2A1 breast cancer cell line models in vivo and/or in vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model. In vitro, we show that D2.OR and ZR-75-1 cells in response to a 3D environment or serum-free conditions are growth-arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.

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