Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition.
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.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Min
M
Yu
Aditya
A
Bardia
Ben S
BS
Wittner
Shannon L
SL
Stott
Malgorzata E
ME
Smas
David T
DT
Ting
Steven J
SJ
Isakoff
Jordan C
JC
Ciciliano
Marissa N
MN
Wells
Ajay M
AM
Shah
Kyle F
KF
Concannon
Maria C
MC
Donaldson
Lecia V
LV
Sequist
Elena
E
Brachtel
Dennis
D
Sgroi
Jose
J
Baselga
Sridhar
S
Ramaswamy
Mehmet
M
Toner
Daniel A
DA
Haber
Shyamala
S
Maheswaran
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D002452:Cell Count; D002465:Cell Movement; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta