Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity.
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.
['Beerling|Evelyne|E|', 'Seinstra|Daniëlle|D|', 'de Wit|Elzo|E|', 'Kester|Lennart|L|', 'van der Velden|Daphne|D|', 'Maynard|Carrie|C|', 'Schäfer|Ronny|R|', 'van Diest|Paul|P|', 'Voest|Emile|E|', 'van Oudenaarden|Alexander|A|', 'Vrisekoop|Nienke|N|', 'van Rheenen|Jacco|J|']
D000818:Animals D000952:Antigens, Polyomavirus Transforming D001943:Breast Neoplasms D015820:Cadherins D044584:Carcinoma, Ductal D004195:Disease Models, Animal D058750:Epithelial-Mesenchymal Transition D005260:Female D005434:Flow Cytometry D006801:Humans D007150:Immunohistochemistry D008175:Lung Neoplasms D051379:Mice D018345:Mice, Knockout D016513:Mice, SCID D014411:Neoplastic Stem Cells D034622:RNA Interference D034741:RNA, Small Interfering D060888:Real-Time Polymerase Chain Reaction D015375:Receptors, Interleukin-2
epithelial-to-mesenchymal transition (EMT) intravital microscopy cancer