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  • Response to Letter to the Editor
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Response

Response to Sehgal

Oncogene volume 29, pages 2601–2603 (2010)Cite this article

Subjects

We would like to thank Dr Sehgal for his dissenting opinion on the novelty of our recent publication in the 2009 Oncogene issue (Sullivan et al., 2009), and we recognize the importance of the pioneering work by Tamm, Sehgal, and colleagues (Tamm et al., 1989, 1991a, 1991b, 1994a, 1994b, 1998; Krueger et al., 1991; Sehgal and Tamm, 1991) for many aspects of interleukin-6 (IL-6) biology. However, we disagree with the assertions made by Dr Sehgal that a previous body of work has established a phenotypic or a biological signature of epithelial–mesenchymal transition (EMT).

First and foremost, we feel it is prudent to clearly define the process of EMT. For example, is it sufficient to define EMT as a change in cellular localization of E-cadherin in 2D culture with the observed biological responses of cell detachment and decreased cell proliferation? As detailed in the introduction of our 2009 Oncogene publication (Sullivan et al., 2009), we cited multiple studies that focused on the EMT process in cancer. One of these citations, a recent review by Yang and Weinberg, details the EMT processes associated with development and cancer (Yang and Weinberg, 2008). From this review, a historical and current definition of EMT is described. We will summarize the details and definitions that are pertinent for this discussion. As stated, EMT was defined in the 1980s following a series of 3D culture studies (Greenburg and Hay, 1982, 1986, 1988). These studies provided a first definition of EMT based on changes in cellular properties that altered the functional relationship between epithelial cells, the underlying basal lamina and the extracellular matrix (ECM). These properties included epithelial cell elongation and acquisition of a mesenchymal morphology (pseudopodia/filapodia), cell–cell detachment (epithelial cell disassociation) and cell migration. Subsequent cellular and molecular cell studies have further refined the definition and process of EMT. EMT is defined as a dynamic process characterized by morphological changes (epithelial to mesenchymal) associated with distinct changes in cell differentiation markers, including a loss of cell–cell junctions (for example, CDH1), changes in cytokeratin intermediate filaments, acquisition of mesenchymal markers (for example, Vimentin, N-cadherin) and expression of EMT-inducing transcription factors (for example, Twist, Snail, Slug). In addition, functional changes in epithelial cells that confer an ability to invade across the ECM are a functional hallmark of EMT. Epithelial cells, which undergo EMT, demonstrate altered cellular characteristics, acquire enhanced motility/invasiveness and develop unique interactions with the extracellular microenvironment (for example, ECM).

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  1. A Division of Johnson & Johnson, Oncology Biomarkers, Janssen Pharmaceutica, Beerse, Belgium

    B Hall

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Hall, B. Response to Sehgal. Oncogene 29, 2601–2603 (2010). https://doi.org/10.1038/onc.2010.45

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