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PMID: 23372014 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition.

Science (New York, N.Y.) ·Vol. 339 ·No. 6119 ·2013-02-01 ·Pages 580-4

Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S

Abstract

Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

MeSH Terms
Animals Biomarkers, Tumor/genetics,metabolism Breast Neoplasms/blood,genetics,pathology Cell Count Cell Movement Epithelial Cells/pathology Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic Humans Mesoderm/pathology Mice Neoplasm Transplantation Neoplastic Cells, Circulating/metabolism,pathology RNA, Neoplasm/chemistry,genetics Transcription, Genetic Transforming Growth Factor beta/genetics,metabolism
Chemicals
Biomarkers, Tumor RNA, Neoplasm Transforming Growth Factor beta
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Yu Min
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Bardia Aditya
Wittner Ben S
Stott Shannon L
Smas Malgorzata E
Ting David T
Isakoff Steven J
Ciciliano Jordan C
Wells Marissa N
Shah Ajay M
Concannon Kyle F
Donaldson Maria C
Sequist Lecia V
Brachtel Elena
Sgroi Dennis
Baselga Jose
Ramaswamy Sridhar
Toner Mehmet
Haber Daniel A
Maheswaran Shyamala
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1228522
Published
2013-02-01
Pages
580-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3760262
Subset
IM
Grants
NCI NIH HHS · R01 CA129933 · United States
NIBIB NIH HHS · EB008047 · United States
Howard Hughes Medical Institute · United States
NIBIB NIH HHS · U01 EB012493 · United States
NIBIB NIH HHS · R01 EB008047 · United States
NCI NIH HHS · NCI CA129933 · United States
NCI NIH HHS · K12 CA087723 · United States
Databases
GEO
GSE41245
Corrections
CommentIn
PMID: 23407577
CommentIn
PMID: 23419957
CommentIn
PMID: 23518345
ErratumIn
PMID: 30679345
External Links
PubMed source DOI: 10.1126/science.1228522 PMC Full Text View journal details
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