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Transcommitment: Paving the Way to Barrett’s Metaplasia

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Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 908))

Abstract

Barrett’s esophagus is the condition in which metaplastic columnar epithelium that predisposes to cancer development replaces stratified squamous epithelium in the distal esophagus. Potential sources for the cell or tissue of origin for metaplastic Barrett’s epithelium are reviewed including native esophageal differentiated squamous cells, progenitor cells native to the esophagus located within the squamous epithelium or in the submucosal glands or ducts, circulating bone marrow-derived stem cells, and columnar progenitor cells from the squamocolumnar junction or the gastric cardia that proximally shift into the esophagus to fill voids left by damaged squamous epithelium. Wherever its source the original cell must undergo molecular reprogramming (i.e., either transdifferentiation or transcommitment) to give rise to specialized intestinal metaplasia. Transcription factors that specify squamous, columnar, intestinal, and mucus-secreting epithelial differentiation are discussed. An improved understanding of how esophageal columnar metaplasia forms could lead to development of effective treatment or prevention strategies for Barrett’s esophagus. It could also more broadly inform upon normal tissue development and differentiation, wound healing, and stem cell biology.

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Funding

This work was funded by the US National Institutes of Health (R01-DK097340 to D.H.W. and R01-DK63621 to R.F.S.) and by the Office of Research and Development, US Department of Veterans Affairs (I01-BX001061 and I01-BX002666 to R.F.S.).

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, Esophageal Diseases Center, Medical Service, VA North Texas Health Care System, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8852, USA

    David H. Wang M.D., Ph.D.

  2. Division of Digestive and Liver Diseases, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, Esophageal Diseases Center, Medical Service (111B1), VA North Texas Health Care System, University of Texas Southwestern Medical Center, 4500 S. Lancaster Road, Dallas, TX, 75216, USA

    Rhonda F. Souza M.D.

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  1. David H. Wang M.D., Ph.D.
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  2. Rhonda F. Souza M.D.
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Correspondence to David H. Wang M.D., Ph.D. .

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Editors and Affiliations

  1. UCL Cancer Institute, University College London, London, United Kingdom

    Marnix Jansen

  2. Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

    Nicholas A. Wright

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Wang, D.H., Souza, R.F. (2016). Transcommitment: Paving the Way to Barrett’s Metaplasia. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_10

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