Patient-Derived Scaffolds of Colorectal Cancer Metastases as an Organotypic 3D Model of the Liver Metastatic Microenvironment.
3D culture model
decellularization
disease modeling
drug test
extracellular matrix
liver metastasis
microenvironment
response to treatment
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
05 Feb 2020
05 Feb 2020
Historique:
received:
04
12
2019
revised:
03
02
2020
accepted:
04
02
2020
entrez:
9
2
2020
pubmed:
9
2
2020
medline:
9
2
2020
Statut:
epublish
Résumé
The liver is the most common site for colorectal cancer (CRC) metastasis and there is an urgent need for new tissue culture models to study colorectal cancer liver metastasis (CRLM) as current models do not mimic the biological, biochemical, and structural characteristics of the metastatic microenvironment. Decellularization provides a novel approach for the study of the cancer extracellular matrix (ECM) as decellularized scaffolds retain tissue-specific features and biological properties. In the present study, we created a 3D model of CRC and matched CRLM using patient-derived decellularized ECM scaffolds seeded with the HT-29 CRC cell line. Here, we show an increased HT-29 cell proliferation and migration capability when cultured in cancer-derived scaffolds compared to same-patient healthy colon and liver tissues. HT-29 cells cultured in CRLM scaffolds also displayed an indication of epithelial-mesenchymal transition (EMT), with a loss of E-cadherin and increased Vimentin expression. EMT was confirmed by gene expression profiling, with the most represented biological processes in CRLM-seeded scaffolds involving demethylation, deacetylation, a cellular response to stress metabolic processes, and a response to the oxygen level and starvation. HT-29 cells cultured in cancer-specific 3D microenvironments showed a reduced response to treatment with 5-fluorouracil and 5-fluorouracil combined with Irinotecan when used at a standard IC
Identifiants
pubmed: 32033473
pii: cancers12020364
doi: 10.3390/cancers12020364
pmc: PMC7072130
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Fondazione Cassa di Risparmio di Padova e Rovigo
ID : Pediatric Rsesarch
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : Fellowship for Italy: 19486
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : Investigator Grant: 19104
Organisme : Regione del Veneto
ID : LIFELAB Program
Déclaration de conflit d'intérêts
The authors declare no potential conflicts of interest.
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