1. Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity.
- Author
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Beerling E, Seinstra D, de Wit E, Kester L, van der Velden D, Maynard C, Schäfer R, van Diest P, Voest E, van Oudenaarden A, Vrisekoop N, and van Rheenen J
- Subjects
- Animals, Antigens, Polyomavirus Transforming genetics, Antigens, Polyomavirus Transforming metabolism, Breast Neoplasms etiology, Breast Neoplasms metabolism, Cadherins antagonists & inhibitors, Cadherins genetics, Cadherins metabolism, Carcinoma, Ductal etiology, Carcinoma, Ductal metabolism, Disease Models, Animal, Female, Flow Cytometry, Humans, Immunohistochemistry, Lung Neoplasms pathology, Lung Neoplasms secondary, Mice, Mice, Knockout, Mice, SCID, Neoplastic Stem Cells cytology, RNA Interference, RNA, Small Interfering metabolism, Real-Time Polymerase Chain Reaction, Receptors, Interleukin-2 deficiency, Receptors, Interleukin-2 genetics, Breast Neoplasms pathology, Carcinoma, Ductal pathology, Epithelial-Mesenchymal Transition, Neoplastic Stem Cells metabolism
- Abstract
Forced overexpression and/or downregulation of proteins regulating epithelial-to-mesenchymal transition (EMT) has been reported to alter metastasis by changing migration and stem cell capacity of tumor cells. However, these manipulations artificially keep cells in fixed states, while in vivo cells may adapt transient and reversible states. Here, we have tested the existence and role of epithelial-mesenchymal plasticity in metastasis of mammary tumors without artificially modifying EMT regulators. In these tumors, we found by intravital microscopy that the motile tumor cells have undergone EMT, while their epithelial counterparts were not migratory. Moreover, we found that epithelial-mesenchymal plasticity renders any EMT-induced stemness differences, as reported previously, irrelevant for metastatic outgrowth, because mesenchymal cells that arrive at secondary sites convert to the epithelial state within one or two divisions, thereby obtaining the same stem cell potential as their arrived epithelial counterparts. We conclude that epithelial-mesenchymal plasticity supports migration but additionally eliminates stemness-enhanced metastatic outgrowth differences., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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