Inhibition of BMP2 and BMP4 Represses Barrett’s Esophagus While Enhancing the Regeneration of Squamous Epithelium in Preclinical Models

Correia, Ana C. P.; Straub, Daniëlle; Read, Matthew; Hoefnagel, Sanne; Romero-Pinedo, Salvador; Abadía-Molina, Ana Clara; Clemons, Nicholas J.; Wang, Kenneth; Calpe, Silvia; Phillips, Wayne A.; Krishnadath, Kausilia K.

doi:10.1016/j.jcmgh.2023.01.003

Cited by 5 publications

(4 citation statements)

References 40 publications

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“… 56 However, a recently described tamoxifen-inducible noggin knockout resulted in increased BMP signaling, and columnar metaplasia developed at the SCJ. 57 In this conditional knockout, neocolumnar epithelium developed 4 weeks after noggin deletion, and administration of antibodies to both BMP2 and BMP4 was associated with a shift toward neosquamous epithelium. 57 A different group found that overexpression of GATA4 using a conditional knock-in ( Shh Cre ) in the developing mouse stomach resulted in columnar-like cells in the forestomach.…”

Section: Mouse Modelsmentioning

confidence: 87%

Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma

Martinez-Uribe,

Becker,

Garman

2024

Cellular and Molecular Gastroenterology and Hepatology

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Section: Mouse Modelsmentioning

confidence: 87%

Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma

Martinez-Uribe,

Becker,

Garman

2024

Cellular and Molecular Gastroenterology and Hepatology

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“…This emphasizes the importance of utilizing BMP antagonists to ensure the prolonged maintenance of stem cells in esophageal progenitor cells. However, the scenario may differ when considering EAC organoids, as studies propose that BMP signalling could play a significant role in the development of Barrett’s esophagus and EAC ( Wang et al, 2010 ; Westra et al, 2022 ; Correia et al, 2023 ). Consequently, blocking BMP might not be deemed necessary for EAC PDOs.…”

Section: Establishment and Optimization Of Eac Patient-derived Organo...mentioning

confidence: 99%

Modelling esophageal adenocarcinoma and Barrett’s esophagus with patient-derived organoids

Milne,

Mustafa,

Clemons

2024

Front. Mol. Biosci.

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Currently, esophageal adenocarcinoma (EAC) research is hindered by a dearth of adequate models to study this disease. Traditional cell line and genetically engineered mouse models are lacking in biological and physiological significance, whilst the inefficiency of patient-derived xenografts limit their potential applications. This review describes the landscape of EAC research using patient-derived organoids (PDOs). Here, we detail the methods of establishment and optimization of EAC PDO cultures, as well as current and prospective applications of these models. We further highlight a crucial knowledge gap in the mechanisms of EAC transformation from its precursor lesion, Barrett’s esophagus (BE). As such, we also describe the culture requirements of BE PDOs and attempts to model tumorigenesis using PDO models.

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“…Upon exposure to chronic acid reflux, the HH pathway is also activated in a subset of Keratin 7- and SOX9-expressing squamous cells to trigger squamous-to-columnar conversion and activation of Wnt and BMP pathways [ 35 ]. Upon exposure to acid and bile, increased sonic HH signaling occurs in the BE epithelium that enhances expression of stromal PTCH1, resulting in induction of BMP4 expression [ 36 , 37 ]. BMP4 can then directly signal the epithelium to shift towards a more columnar intestinal phenotype through activation of the transcription factors, SOX9 and FOXA2 [ 38 ].…”

Section: Fibroblasts Mediate Barrett's Esophagus Development and Prog...mentioning

confidence: 99%

The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma

Zhu,

Jin

2024

Current Opinion in Gastroenterology

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Purpose of review Barrett's esophagus (BE) is the number one risk factor for developing esophageal adenocarcinoma (EAC), a deadly cancer with limited treatment options that has been increasing in incidence in the US. In this report, we discuss current studies on the role of mesenchyme and cancer-associated fibroblasts (CAFs) in BE and EAC, and we highlight translational prospects of targeting these cells. Recent findings New insights through studies using single-cell RNA sequencing (sc-RNA seq) have revealed an important emerging role of the mesenchyme in developmental signaling and cancer initiation. BE and EAC share similar stromal gene expression, as functional classifications of nonepithelial cells in BE show a remarkable similarity to EAC CAFs. Several recent sc-RNA seq studies and novel organoid fibroblast co-culture systems have characterized the subgroups of fibroblasts in BE and EAC, and have shown that these cells can directly influence the epithelium to induce BE development and cancer progression. Targeting the CAFs in EAC with may be a promising novel therapeutic strategy. Summary The fibroblasts in the surrounding mesenchyme may have a direct role in influencing altered epithelial plasticity during BE development and progression to EAC.

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Inhibition of BMP2 and BMP4 Represses Barrett’s Esophagus While Enhancing the Regeneration of Squamous Epithelium in Preclinical Models

Cited by 5 publications

References 40 publications

Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma

Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma

Modelling esophageal adenocarcinoma and Barrett’s esophagus with patient-derived organoids

The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma

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