ArticleNeoplasia (New York, N.Y.)2011
Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.BMC cancer · 2016Trial
- Esophageal adenocarcinoma models: a closer look.Frontiers in molecular biosciences · 2024Review
- Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine.Cellular and molecular gastroenterology and hepatology · 2018Review
- Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population.PloS one · 2018Article
- Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System.The American journal of pathology · 2017Article
- Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.Neoplasia (New York, N.Y.) · 2015Article
- Mechanisms of Barrett's oesophagus: intestinal differentiation, stem cells, and tissue models.Best practice & research. Clinical gastroenterology · 2015Review
- Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.Experimental biology and medicine (Maywood, N.J.) · 2014Review
- Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.International journal of experimental pathology · 2014Article
- Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Barrett esophagus: history, definition and etiopathogeny.Journal of medicine and life · 2014Review
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
- Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction.Cancer biology & therapy · 2013Review
- Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems.Stem cell research & therapy · 2013Review
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20.Digestive diseases and sciences · 2012Article
- The interconnectedness of cancer cell signaling.Neoplasia (New York, N.Y.) · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The incidence of esophageal adenocarcinoma (EAC) is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE). BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2) are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.