E-cadherin re-expression shows in vivo evidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells.
Substantial experimental evidence has shown that dedifferentiation from an epithelial state to a mesenchymal-like state (EMT) drives tumor cell metastasis. This transition facilitates tumor cells to acquire motility and invasive features. Intriguingly, tumor cells at the metastatic site are primarily epithelial, and it is believed that they differentiate back to an epithelial state by a process called mesenchymal to epithelial transition (MET). However, there is little in vivo evidence to support the MET process. To investigate EMT and MET in vivo, we generated two epithelial (E) and two mesenchymal (M) primary clonal cell lines from a spontaneous mouse mammary tumor (Tg MMTV/neu). These cells were labeled with reporters (GFP and luciferase), and tracked in vivo during primary tumor growth and subsequent secondary metastasis. Once E cells were implanted into the mammary fat pad, E-cadherin expression progressively decreased and continued to decrease as the primary tumor enlarged over time. A greater percentage of E tumor cells expressed E-cadherin at the secondary metastatic site as compared to the corresponding primary tumor site. Collectively, these data provide direct in vivo evidence that epithelial tumor cells have metastatic potential, undergo EMT at the primary tumor site, and MET at the metastatic site.
Department of Pediatrics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Katie
K
Palen
Department of Pediatrics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
James
J
Weber
Department of Microbiology and Molecular Genetics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Michael B
MB
Dwinell
Department of Pediatrics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Bryon D
BD
Johnson
Department of Pediatrics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.|Department of Obstetrics and Gynecology at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Ramani
R
Ramchandran
Department of Pediatrics at The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Jill A
JA
Gershan
D000818:Animals; D001940:Breast / Q000166:cytology / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002999:Clone Cells / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D061251:Primary Cell Culture; D013154:Spleen / Q000473:pathology
D015820:Cadherins; C000611838:Cdh1 protein, mouse
E-cadherin; EMT; MET; breast cancer; metastasis