Transcriptional regulation by normal epithelium of premalignant to malignant progression in Barrett's esophagus

Jia Zeng, Laimonas Kelbauskas, Aida Rezaie, Kristen Lee, Benjamin Ueberroth, Weimin Gao, Dmitry Derkach, Thai Tran, Dean Smith, Kimberly J. Bussey, Deirdre Meldrum

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Abstract

In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett's esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts.

Original languageEnglish (US)
Article number35227
JournalScientific reports
Volume6
DOIs
StatePublished - Oct 12 2016

ASJC Scopus subject areas

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    Zeng, J., Kelbauskas, L., Rezaie, A., Lee, K., Ueberroth, B., Gao, W., Derkach, D., Tran, T., Smith, D., Bussey, K. J., & Meldrum, D. (2016). Transcriptional regulation by normal epithelium of premalignant to malignant progression in Barrett's esophagus. Scientific reports, 6, [35227]. https://doi.org/10.1038/srep35227