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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1470379
This article is part of the Research Topic Cancer Plasticity and The Microenvironment: Implications for Immunity and Therapy Response: Volume II View all 13 articles
Modeling Epithelial-Mesenchymal Transition in Patient-Derived Breast Cancer Organoids
Provisionally accepted
Neta Bar-Hai
1,2
Rakefet Ben-Yishay
1
Sheli Arbili-Yarhi
1*
Naama Herman
3*
Vered Avidan- Noy
3*
Tehillah Menes
2,3*
Aiham Mansour
3*
Fahim Awwad
3*
Nora Balint-Lahat
4*
Gil Goldinger
4*
Goni Hout-Siloni
4*
Mohammad Adileh
5*
Raanan Berger
1,2*
Dana Ishay-Ronen
1,2*- 1 Oncology institute, Shaba Medical Center, Tel-Hashomer, Israel
- 2 Affiliated with faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 3 Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
- 4 Institute of Pathology, Shaba Medical Center, Tel-Hashomer, Israel
- 5 Hadassah Medical Center, Jerusalem, Jerusalem, Israel
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.
Keywords: breast cancer, EMT, Cell plasticity, tumor heterogeneity, Organoids 4090, Figure Count: 10, Table Count: 2
Received: 25 Jul 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 Bar-Hai, Ben-Yishay, Arbili-Yarhi, Herman, Avidan- Noy, Menes, Mansour, Awwad, Balint-Lahat, Goldinger, Hout-Siloni, Adileh, Berger and Ishay-Ronen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sheli Arbili-Yarhi, Oncology institute, Shaba Medical Center, Tel-Hashomer, Israel
Naama Herman, Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
Vered Avidan- Noy, Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
Tehillah Menes, Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
Aiham Mansour, Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
Fahim Awwad, Department of General Surgery Shaba Medical Center, Tel-Hashomer, Israel
Nora Balint-Lahat, Institute of Pathology, Shaba Medical Center, Tel-Hashomer, Israel
Gil Goldinger, Institute of Pathology, Shaba Medical Center, Tel-Hashomer, Israel
Goni Hout-Siloni, Institute of Pathology, Shaba Medical Center, Tel-Hashomer, Israel
Mohammad Adileh, Hadassah Medical Center, Jerusalem, 9112001, Jerusalem, Israel
Raanan Berger, Oncology institute, Shaba Medical Center, Tel-Hashomer, Israel
Dana Ishay-Ronen, Oncology institute, Shaba Medical Center, Tel-Hashomer, Israel
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