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PMID: 18485877 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The epithelial-mesenchymal transition generates cells with properties of stem cells.

Cell ·Vol. 133 ·No. 4 ·2008-05-16 ·Pages 704-15

Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA

Abstract

The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.

MeSH Terms
Adult Stem Cells/cytology Animals CD24 Antigen/metabolism Cell Transformation, Neoplastic Cells, Cultured Epithelial Cells/cytology Humans Hyaluronan Receptors/metabolism Mammary Glands, Animal/cytology Mammary Glands, Human/cytology Mesoderm/cytology,metabolism Mice Neoplastic Stem Cells/cytology Spheroids, Cellular Stem Cells/cytology Tumor Cells, Cultured
Chemicals
CD24 Antigen Hyaluronan Receptors
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Mani Sendurai A
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. smani@mdanderson.org
Guo Wenjun
Liao Mai-Jing
Eaton Elinor Ng
Ayyanan Ayyakkannu
Zhou Alicia Y
Brooks Mary
Reinhard Ferenc
Zhang Cheng Cheng
Shipitsin Michail
Campbell Lauren L
Polyak Kornelia
Brisken Cathrin
Yang Jing
Weinberg Robert A
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.03.027
Email
smani@mdanderson.org
Published
2008-05-16
Pages
704-15
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2728032
Subset
IM
Grants
NCI NIH HHS · R01-CA078461 · United States
NCI NIH HHS · P01 CA080111 · United States
NCI NIH HHS · P50 CA089393-080014 · United States
NCI NIH HHS · P01 CA080111-09 · United States
NCI NIH HHS · R01 CA116235-02 · United States
NCI NIH HHS · CA94074 · United States
NCI NIH HHS · CA89393 · United States
NCI NIH HHS · P0-CA080111 · United States
NCI NIH HHS · R01 CA116235-01A1 · United States
NCI NIH HHS · R01 CA116235-03 · United States
NCI NIH HHS · P50 CA089393 · United States
NCI NIH HHS · R01 CA116235 · United States
NCI NIH HHS · P50 CA089393-070014 · United States
NCI NIH HHS · R01 CA078461 · United States
NCI NIH HHS · P50 CA089393-060014 · United States
NCI NIH HHS · R01 CA094074 · United States
NCI NIH HHS · R01 CA078461-09 · United States
Corrections
CommentIn
PMID: 18522839
CommentIn
PMID: 20551963
External Links
PubMed source DOI: 10.1016/j.cell.2008.03.027 PMC Full Text View journal details
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