Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Botelho, Natalia K.; Schneiders, F; Lord, Sarah J.; Freeman, Anthony; Tyagi, Sonika; Nancarrow, Derek J.; Hayward, Nicholas K.; Whiteman, David C.; Lord, Reginald V.

doi:10.4161/cbt.10.2.12166

Cited by 21 publications

(21 citation statements)

References 47 publications

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“…1E). We probed the metaplasia and control tissues for known markers (Wang et al, 2009; Botelho et al, 2010) of Barrett's esophagus using antibodies against villin (Vil1) and anterior gradient 2 (Agr2) in addition to keratin 8 (Krt8), all of which showed specific and robust staining of the metaplasia in the p63 null embryos (Figure S1). The histological similarity between the observed metaplasia in p63 null embryos and Barrett's esophagus in humans drove us to investigate these tissues at a molecular level.…”

Section: Resultsmentioning

confidence: 99%

“…2E; Table S2). Within these common genes were many of the markers established for Barrett's esophagus and gastric intestinal metaplasia (Wang et al, 2009; Botelho et al, 2010). In fact, the fold-change in these genes in the p63 null metaplasia (mucin 4 (Muc4, 73×), keratin 20 (Krt20, 61×), trefoil factor 2 (TFF2, 49×), claudin 3 (Cldn3, 46×), Agr2 (120×), and Vil1 (27×); p< 10 −5 for all) greatly exceeded those in the Barrett's datasets (Table S2).…”

Section: Resultsmentioning

confidence: 99%

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Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Wang

Ouyang

Yamamoto

et al. 2011

Cell

299

295

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SUMMARY Barrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Triggered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embryonic epithelium that is normally undermined and replaced by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squamocolumnar junction, the source of Barrett's metaplasia. Upon programmed damage to the squamous epithelium, we show that these embryonic cells migrate towards adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Wang

Ouyang

Yamamoto

et al. 2011

Cell

299

295

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“…Secreted protein acidic and rich in cysteine (SPARC) is a protein with multiple effects, including counteradhesive and antiproliferative functions, as well as cell cycle modulation and matrix remodelling properties [43]. SPARC is increased in BO and OAC [44], while its expression is higher in the normal oesophagus of Barrett's and cancer patients compared with healthy patients, suggesting that this may be a field effect in the oesophagus [45,46]. SPARC may be overexpressed in the tumour microenvironment in an attempt to inhibit tumour growth, while tumour cells themselves reduce SPARC.…”

Section: Role Of the Extracellular Matrixmentioning

confidence: 99%

Barretts to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

Picardo¹,

Maher²,

O'Sullivan³

et al. 2012

Dig Surg

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Cancer-related inflammation is considered the ‘seventh hallmark of cancer’; many studies show that tumours develop and progress within inflammatory diseases. This review focuses on Barrett’s oesophagus, a common condition in which chronic inflammation and resulting alterations in the stroma can lead to carcinogenesis, specifically oesophageal adenocarcinoma. Changes that occur in the tissue microenvironment during development of this disease are discussed. Infiltration of immune cells facilitates tumour development through production of factors that promote carcinogenesis and by enabling tumours to evade the host immune response. Small molecules including cytokines, chemokines and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation, and provides structural support to developing tumours. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumourigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients and growth factors to rapidly dividing cells, and providing a mechanism for metastatic spread. The cells and molecules outlined here represent potential targets for treatment of this cancer, especially in its pre-cancerous, inflammatory stage.

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“…It is in this context that COX-2 is thought to contribute to Barrett carcinogenesis. Increased COX-2 expression is detected in the progression from BE to EAC, 69 , 72 , 147 , 148 and is associated with proliferation and reduced survival 149 . However, COX-2 expression appears to be independent of the degree of inflammation, although it is highest in the distal part compared with proximal BE, 150 which is also the most frequent location of EAC.…”

Section: Molecular Pathogenesis Of Eacmentioning

confidence: 99%

Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction

Clemons

Phillips

Lord

2013

Cancer Biology & Therapy

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Esophageal adenocarcinoma develops in response to severe gastroesophageal reflux disease through the precursor lesion Barrett esophagus, in which the normal squamous epithelium is replaced by a columnar lining. The incidence of esophageal adenocarcinoma in the United States has increased by over 600% in the past 40 years and the overall survival rate remains less than 20% in the community. This review highlights some of the signaling pathways for which there is some evidence of a role in the development of esophageal adenocarcinoma. An increasingly detailed understanding of the biology of this cancer has emerged recently, revealing that in addition to the well-recognized alterations in single genes such as p53, p16, APC, and telomerase, there are interactions between the components of the reflux fluid, the homeobox gene Cdx2, and the Wnt, Notch, and Hedgehog signaling pathways.

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Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Cited by 21 publications

References 47 publications

Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Barretts to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction

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Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

Cited by 21 publications

References 47 publications

Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Residual Embryonic Cells as Precursors of a Barrett's-like Metaplasia

Barretts to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction

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Product

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Barretts to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer