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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 7/2011

01-10-2011 | Research Paper

Inducible expression of TGFβ, Snail and Zeb1 recapitulates EMT in vitro and in vivo in a NSCLC model

Authors: Gretchen M. Argast, Joseph S. Krueger, Stuart Thomson, Isabela Sujka-Kwok, Krista Carey, Stacia Silva, Matthew O’Connor, Peter Mercado, Iain J. Mulford, G. David Young, Regina Sennello, Robert Wild, Jonathan A. Pachter, Julie L. C. Kan, John Haley, Maryland Rosenfeld-Franklin, David M. Epstein

Published in: Clinical & Experimental Metastasis | Issue 7/2011

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Abstract

The progression of cancer from non-metastatic to metastatic is the critical transition in the course of the disease. The epithelial to mesenchymal transition (EMT) is a mechanism by which tumor cells acquire characteristics that improve metastatic efficiency. Targeting EMT processes in patients is therefore a potential strategy to block the transition to metastatic cancer and improve patient outcome. To develop models of EMT applicable to in vitro and in vivo settings, we engineered NCI-H358 non-small cell lung carcinoma cells to inducibly express three well-established drivers of EMT: activated transforming growth factor β (aTGFβ), Snail or Zeb1. We characterized the morphological, molecular and phenotypic changes induced by each of the drivers and compared the different end-states of EMT between the models. Both in vitro and in vivo, induction of the transgenes Snail and Zeb1 resulted in downregulation of epithelial markers and upregulation of mesenchymal markers, and reduced the ability of the cells to proliferate. Induced autocrine expression of aTGFβ caused marker and phenotypic changes consistent with EMT, a modest effect on growth rate, and a shift to a more invasive phenotype. In vivo, this manifested as tumor cell infiltration of the surrounding mouse stromal tissue. Overall, Snail and Zeb1 were sufficient to induce EMT in the cells, but aTGFβ induced a more complex EMT, in which changes in extracellular matrix remodeling components were pronounced.
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Metadata
Title
Inducible expression of TGFβ, Snail and Zeb1 recapitulates EMT in vitro and in vivo in a NSCLC model
Authors
Gretchen M. Argast
Joseph S. Krueger
Stuart Thomson
Isabela Sujka-Kwok
Krista Carey
Stacia Silva
Matthew O’Connor
Peter Mercado
Iain J. Mulford
G. David Young
Regina Sennello
Robert Wild
Jonathan A. Pachter
Julie L. C. Kan
John Haley
Maryland Rosenfeld-Franklin
David M. Epstein
Publication date
01-10-2011
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 7/2011
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-011-9394-8

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