AUTHOR=Bar-Hai Neta , Ben-Yishay Rakefet , Arbili-Yarhi Sheli , Herman Naama , Avidan-Noy Vered , Menes Tehillah , Mansour Aiham , Awwad Fahim , Balint-Lahat Nora , Goldinger Gil , Hout-Siloni Goni , Adileh Mohammad , Berger Raanan , Ishay-Ronen Dana 

TITLE=Modeling epithelial-mesenchymal transition in patient-derived breast cancer organoids

JOURNAL=Frontiers in Oncology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1470379

DOI=10.3389/fonc.2024.1470379

ISSN=2234-943X

ABSTRACT=Cellular plasticity is enhanced by dedifferentiation processes such as epithelial-mesenchymal transition (EMT). The dynamic and transient nature of EMT-like processes challenges the investigation of cell plasticity in patient-derived breast cancer models. Here, we utilized patient-derived organoids (PDOs) as a model to study the susceptibility of primary breast cancer cells to EMT. Upon induction with TGF-β, PDOs exhibited EMT-like features, including morphological changes, E-cadherin downregulation and cytoskeletal reorganization, leading to an invasive phenotype. Image analysis and the integration of deep learning algorithms enabled the implantation of microscopy-based quantifications demonstrating repetitive results between organoid lines from different breast cancer patients. Interestingly, epithelial plasticity was also expressed in terms of alterations in luminal and myoepithelial distribution upon TGF-β induction. The effective modeling of dynamic processes such as EMT in organoids and their characteristic spatial diversity highlight their potential to advance research on cancer cell plasticity in cancer patients.