Publication Date:
2013-02-02
Description:
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)-beta pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760262/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760262/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Min -- 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 -- EB008047/EB/NIBIB NIH HHS/ -- K12 CA087723/CA/NCI NIH HHS/ -- NCI CA129933/CA/NCI NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- U01 EB012493/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):580-4. doi: 10.1126/science.1228522.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23372014" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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