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Modeling epithelial-mesenchymal transition in patient-derived breast cancer organoids
oleh: Neta Bar-Hai, Neta Bar-Hai, Rakefet Ben-Yishay, Sheli Arbili-Yarhi, Naama Herman, Vered Avidan-Noy, Tehillah Menes, Tehillah Menes, Aiham Mansour, Fahim Awwad, Nora Balint-Lahat, Gil Goldinger, Gil Goldinger, Goni Hout-Siloni, Mohammad Adileh, Raanan Berger, Raanan Berger, Dana Ishay-Ronen, Dana Ishay-Ronen
Format: | Article |
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Diterbitkan: | Frontiers Media S.A. 2024-10-01 |
Deskripsi
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.