Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing

Abstract FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions,...

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Autores principales: Larisa Tratnjek, Nadica Sibinovska, Slavko Kralj, Darko Makovec, Katja Kristan, Mateja Erdani Kreft
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/71ed6df8a9fa45b7b60a7a4a76dac028
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spelling oai:doaj.org-article:71ed6df8a9fa45b7b60a7a4a76dac0282021-12-02T13:24:25ZStandardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing10.1038/s41598-021-85530-w2045-2322https://doaj.org/article/71ed6df8a9fa45b7b60a7a4a76dac0282021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85530-whttps://doaj.org/toc/2045-2322Abstract FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions, we performed a thorough characterization of the FLO-1 cell line under different culturing conditions with the aim of (1) examining the effect of serum-free growth medium and air–liquid interface (A–L) culturing, which better reflect physiological conditions in vivo and (2) investigating the differentiation potential of FLO-1 cells to mimic the properties of the in vivo esophageal epithelium. Our study shows that the composition of the media influenced the morphological, ultrastructural and molecular characteristics of FLO-1 cells, such as the expression of junctional proteins. Importantly, FLO-1 cells formed spheres at the A–L interface, recapitulating key elements of tumors in the esophageal tube, i.e., direct contact with the gas phase and three-dimensional architecture. On the other hand, FLO-1 models exhibited high permeability to model drugs and zero permeability markers, and low transepithelial resistance, and therefore poorly mimicked normal esophageal epithelium. In conclusion, the identified effect of culture conditions on the characteristics of FLO-1 cells should be considered for standardization, data reproducibility and validity of the in vitro EAC model. Moreover, the sphere-forming ability of FLO-1 cells at the A–L interface should be considered in EAC tumor biology and anticancer drug studies as a reliable and straightforward model with the potential to increase the predictive efficiency of the current in vitro approaches.Larisa TratnjekNadica SibinovskaSlavko KraljDarko MakovecKatja KristanMateja Erdani KreftNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-23 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Larisa Tratnjek
Nadica Sibinovska
Slavko Kralj
Darko Makovec
Katja Kristan
Mateja Erdani Kreft
Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
description Abstract FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions, we performed a thorough characterization of the FLO-1 cell line under different culturing conditions with the aim of (1) examining the effect of serum-free growth medium and air–liquid interface (A–L) culturing, which better reflect physiological conditions in vivo and (2) investigating the differentiation potential of FLO-1 cells to mimic the properties of the in vivo esophageal epithelium. Our study shows that the composition of the media influenced the morphological, ultrastructural and molecular characteristics of FLO-1 cells, such as the expression of junctional proteins. Importantly, FLO-1 cells formed spheres at the A–L interface, recapitulating key elements of tumors in the esophageal tube, i.e., direct contact with the gas phase and three-dimensional architecture. On the other hand, FLO-1 models exhibited high permeability to model drugs and zero permeability markers, and low transepithelial resistance, and therefore poorly mimicked normal esophageal epithelium. In conclusion, the identified effect of culture conditions on the characteristics of FLO-1 cells should be considered for standardization, data reproducibility and validity of the in vitro EAC model. Moreover, the sphere-forming ability of FLO-1 cells at the A–L interface should be considered in EAC tumor biology and anticancer drug studies as a reliable and straightforward model with the potential to increase the predictive efficiency of the current in vitro approaches.
format article
author Larisa Tratnjek
Nadica Sibinovska
Slavko Kralj
Darko Makovec
Katja Kristan
Mateja Erdani Kreft
author_facet Larisa Tratnjek
Nadica Sibinovska
Slavko Kralj
Darko Makovec
Katja Kristan
Mateja Erdani Kreft
author_sort Larisa Tratnjek
title Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
title_short Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
title_full Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
title_fullStr Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
title_full_unstemmed Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
title_sort standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/71ed6df8a9fa45b7b60a7a4a76dac028
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