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An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
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Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy
Xilal Y Rima1,2,3, Sarmila Majumder3,4, Divya S Patel1
1William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, USA.
Advanced Healthcare Materials
|May 20, 2026
Summary
Invasive lobular carcinoma (ILC) cells can enter a dormant state, contributing to late recurrences. Understanding this dormancy and anti-estrogen resistance is key for improving ILC patient outcomes.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Biology
Background:
- Invasive lobular carcinoma (ILC) comprises 10-15% of breast cancers.
- Disseminated tumor cells (DTCs) and therapy resistance pose significant risks for ILC patients.
- Late recurrences in ILC suggest a role for dormant DTCs.
Purpose of the Study:
- To investigate the link between anti-estrogen resistance and dormancy in ILC.
- To develop and utilize advanced in vitro models for ILC research.
Main Methods:
- Employed multidimensional, micro-compartmentalized in vitro models.
- Engineered platforms mimicked ILC morphology, distinguishing it from invasive ductal carcinoma (IDC).
- Induced reversible dormancy to study epigenetic and sensing changes.
Main Results:
- Bioengineered models successfully recapitulated ILC characteristics.
- Induced dormancy in anti-estrogen-resistant ILC cells revealed epigenetic alterations.
- Enhanced substrate sensing (chemical and mechanical) was observed in dormant ILC cells, mediated by p27Kip1 signaling.
Conclusions:
- A novel in vitro platform facilitates the study of ILC dormancy and anti-estrogen resistance.
- p27Kip1 signaling is crucial in the dormant, resistant ILC phenotype.
- This approach offers a high-throughput method for expedited ILC dormancy investigation.
