A combinatorial culture strategy to develop pseudomyxoma peritonei organoid models.
3D models
appendiceal tumors
mucin
organoids
pseudomyxoma peritonei
Journal
Journal of surgical oncology
ISSN: 1096-9098
Titre abrégé: J Surg Oncol
Pays: United States
ID NLM: 0222643
Informations de publication
Date de publication:
03 Oct 2024
03 Oct 2024
Historique:
received:
15
07
2024
accepted:
15
08
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
3
10
2024
Statut:
aheadofprint
Résumé
Few preclinical models of pseudomyxoma peritonei (PMP) have been developed, probably due to the tumor's low incidence and its peculiar characteristics of slow growth. Therefore, there is a need to develop more refined PMP models that better reflect its characteristics. The aim of the study is to develop a culture strategy to generate organoid models derived from PMP patient samples. We followed a strategy based on combinatorial culture conditions that include the different factors essential for PMP growth and that mimic the microenvironment present in the patients. We cultured PMP samples in the presence of the various factors produced by the niche environment of PMP. We obtained 12 PMP organoid models, each of which grows under specific culture conditions. PMP-derived organoids show long-term expansion capacity and reproduce the genetic landscape and histological phenotype of the tumor of origin. The organoids we developed faithfully reproduce the key features of PMP disease and will allow us to understand the biology of PMP. With them, we will be able to identify key regulatory networks that support PMP progression, providing a platform for multilevel preclinical testing, identify novel diagnostic biomarkers, and generate novel targets for patient treatments.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Few preclinical models of pseudomyxoma peritonei (PMP) have been developed, probably due to the tumor's low incidence and its peculiar characteristics of slow growth. Therefore, there is a need to develop more refined PMP models that better reflect its characteristics. The aim of the study is to develop a culture strategy to generate organoid models derived from PMP patient samples.
METHODS
METHODS
We followed a strategy based on combinatorial culture conditions that include the different factors essential for PMP growth and that mimic the microenvironment present in the patients.
RESULTS
RESULTS
We cultured PMP samples in the presence of the various factors produced by the niche environment of PMP. We obtained 12 PMP organoid models, each of which grows under specific culture conditions. PMP-derived organoids show long-term expansion capacity and reproduce the genetic landscape and histological phenotype of the tumor of origin.
CONCLUSION
CONCLUSIONS
The organoids we developed faithfully reproduce the key features of PMP disease and will allow us to understand the biology of PMP. With them, we will be able to identify key regulatory networks that support PMP progression, providing a platform for multilevel preclinical testing, identify novel diagnostic biomarkers, and generate novel targets for patient treatments.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 27619
Organisme : Accelerator Award 2019
ID : AIRC 24285
Informations de copyright
© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.
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