E-cadherin re-expression shows in vivo evidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells. Oncotarget 2016 Jul 12;7(28):43363-43375
Date
06/09/2016Pubmed ID
27270319Pubmed Central ID
PMC5190029DOI
10.18632/oncotarget.9715Scopus ID
2-s2.0-84978710944 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
Palen K, Weber J, Dwinell MB, Johnson BD, Ramchandran R, Gershan JAAuthors
Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinBryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBreast
Cadherins
Cell Line, Tumor
Cell Movement
Clone Cells
Epithelial Cells
Epithelial-Mesenchymal Transition
Female
Flow Cytometry
Gene Expression Regulation, Neoplastic
Liver Neoplasms, Experimental
Lung Neoplasms
Mammary Neoplasms, Experimental
Mice
Microarray Analysis
Neoplasm Invasiveness
Primary Cell Culture
Spleen
