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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Nature Portfolio
2021
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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) |
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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 |
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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 |
work_keys_str_mv |
AT larisatratnjek standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting AT nadicasibinovska standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting AT slavkokralj standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting AT darkomakovec standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting AT katjakristan standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting AT matejaerdanikreft standardizationofesophagealadenocarcinomainvitromodelanditsapplicabilityformodeldrugtesting |
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