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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

06/09/2016

Pubmed ID

27270319

Pubmed Central ID

PMC5190029

DOI

10.18632/oncotarget.9715

Scopus ID

2-s2.0-84978710944   7 Citations

Abstract

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 JA

Authors

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Bryon D. Johnson PhD 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

Animals
Breast
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
jenkins-FCD Prod-410 e9586552fe7f53c71f7923aa6e27aeabbd3c2473