Patient-derived tumor organoid and fibroblast assembloid models for interrogation of the tumor microenvironment in esophageal adenocarcinoma

The tumor microenvironment (TME) comprises all non-tumor elements of cancer and strongly influences disease progression and phenotype. To understand tumor biology and accurately test new therapeutic strategies, representative models should contain both tumor cells and normal cells of the TME. Here, we describe and characterize co-culture tumor-derived organoids and cancer-associated fibroblasts (CAFs), a major component of the TME, in matrix-embedded assembloid models of esophageal adenocarcinoma (EAC). We demonstrate that the assembloid models faithfully recapitulate the differentiation status of EAC and different CAF phenotypes found in the EAC patient TME. We evaluate cell phenotypes by combining tissue-clearing techniques with whole-mount immunofluorescence and histology, providing a practical framework for the characterization of cancer assembloids.

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Publication Details

Journal
Cell Reports Methods
Published
2024-11-27
DOI
https://doi.org/10.1016/j.crmeth.2024.100909
Citations
10
Primary Topic
Cancer Cells and Metastasis
Type
article
Field-Weighted Citation Impact
2.83

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article

Patient-derived tumor organoid and fibroblast assembloid models for interrogation of the tumor microenvironment in esophageal adenocarcinoma

Zoë S. Walters, Tim Underwood, Benjamin P. Sharpe, Carmen Tse et al.
10 citations
Cell Reports Methods
Cancer Cells and Metastasis
2.83
article

Patient-derived tumor organoid and fibroblast assembloid models for interrogation of the tumor microenvironment in esophageal adenocarcinoma

Zoë S. Walters, Tim Underwood, Benjamin P. Sharpe, Carmen Tse, Oliver Pickering, Matthew Rose‐Zerilli, Jack Harrington, David A. Johnston, Jaya Thomas, Liliya Nazlamova, Rhianna R R Blyth, Ben Grace, Rushda Rajak
article en
10 citations

Abstract

The tumor microenvironment (TME) comprises all non-tumor elements of cancer and strongly influences disease progression and phenotype. To understand tumor biology and accurately test new therapeutic strategies, representative models should contain both tumor cells and normal cells of the TME. Here, we describe and characterize co-culture tumor-derived organoids and cancer-associated fibroblasts (CAFs), a major component of the TME, in matrix-embedded assembloid models of esophageal adenocarcinoma (EAC). We demonstrate that the assembloid models faithfully recapitulate the differentiation status of EAC and different CAF phenotypes found in the EAC patient TME. We evaluate cell phenotypes by combining tissue-clearing techniques with whole-mount immunofluorescence and histology, providing a practical framework for the characterization of cancer assembloids.

Cell Reports MethodsVol. 4(12)
University Hospital Southampton NHS Foundation Trust (GB), University of Southampton (GB)
Wellcome Trust, University Hospital Southampton NHS Foundation Trust, Cancer Research UK, Royal College of Surgeons of England, University of Southampton
Zero hunger
Openalex Percentile: Top 7%
Cancer Cells and Metastasis
2.83
DOIOpen Access PDFOpenAlex
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