Epithelial‐Mesenchymal Transition‐Derived Cells Exhibit Multilineage Differentiation Potential Similar to Mesenchymal Stem Cells
The epithelial‐to‐mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows breast epithelial cells with stem cell traits. In this report, we have further characterized the EMT‐derived cells and shown t...
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| Published in: | Stem cells (Dayton, Ohio) Vol. 28; no. 8; pp. 1435 - 1445 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01-08-2010
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | The epithelial‐to‐mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows breast epithelial cells with stem cell traits. In this report, we have further characterized the EMT‐derived cells and shown that these cells are similar to mesenchymal stem cells (MSCs) with the capacity to differentiate into multiple tissue lineages. For this purpose, we induced EMT by ectopic expression of Twist, Snail, or transforming growth factor‐β in immortalized human mammary epithelial cells. We found that the EMT‐derived cells and MSCs share many properties including the antigenic profile typical of MSCs, that is, CD44+, CD24−, and CD45−. Conversely, MSCs express EMT‐associated genes, such as Twist, Snail, and mesenchyme forkhead 1 (FOXC2). Interestingly, CD140b (platelet‐derived growth factor receptor‐β), a marker for naive MSCs, is exclusively expressed in EMT‐derived cells and not in their epithelial counterparts. Moreover, functional analyses revealed that EMT‐derived cells but not the control cells can differentiate into alizarin red S‐positive mature osteoblasts, oil red O‐positive adipocytes and alcian blue‐positive chondrocytes similar to MSCs. We also observed that EMT‐derived cells but not the control cells invade and migrate towards MDA‐MB‐231 breast cancer cells similar to MSCs. In vivo wound homing assays in nude mice revealed that the EMT‐derived cells home to wound sites similar to MSCs. In conclusion, we have demonstrated that the EMT‐derived cells are similar to MSCs in gene expression, multilineage differentiation, and ability to migrate towards tumor cells and wound sites. STEM CELLS 2010;28:1435–1445 |
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| Bibliography: | First published online in STEM CELLS Author contributions: V.L.B.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; K.E.: collection and assembly of data, data analysis and interpretation, manuscript writing; B.G.H.: collection and assembly of data; Y.S.: collection and assembly of data; F.C.M.: collection and assembly of data, provision of study material; A.A.: collection and assembly of data, provision of study material; R.W.: collection and assembly of data, provision of study material; C.B.: provision of study material; M.A.: conception and design, data analysis and interpretation, financial support, final approval of the manuscript; S.A.M.: conception and design, data analysis and interpretation, financial support, manuscript writing, final approval of the manuscript. Disclosure of potential conflicts of interest is found at the end of this article. Telephone: 1‐713‐792‐9638; Fax: 1‐713‐834‐6082 EXPRESS June 22, 2010. |
| ISSN: | 1066-5099 1549-4918 |
| DOI: | 10.1002/stem.467 |