A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models
Patient-derived xenograft (PDX) models allow for personalized drug selection and the identification of drug resistance mechanisms in cancer cells. However, PDX models present technical disadvantages, such as long engraftment time, low success rate, and high maintenance cost. On the other hand, tumor...
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doaj-fa4e1f8b95e14f7295b6fbc5f3353dd22020-11-25T03:26:34ZengMDPI AGCancers2072-66942020-05-01121304130410.3390/cancers12051304A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft ModelsRobson Amaral0Maike Zimmermann1Ai-Hong Ma2Hongyong Zhang3Kamilla Swiech4Chong-Xian Pan5Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 14040-903 Sao Paulo, BrazilDepartment of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical School, Sacramento, CA 95817, USADepartment of Urology, UC Davis Comprehensive Cancer Center, University of California Davis Medical School, Sacramento, CA 95817, USADepartment of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical School, Sacramento, CA 95817, USADepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 14040-903 Sao Paulo, BrazilDepartment of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical School, Sacramento, CA 95817, USAPatient-derived xenograft (PDX) models allow for personalized drug selection and the identification of drug resistance mechanisms in cancer cells. However, PDX models present technical disadvantages, such as long engraftment time, low success rate, and high maintenance cost. On the other hand, tumor spheroids are emerging as an in vitro alternative model that can maintain the phenotype of cancer cells long enough to perform all assays and predict a patient’s outcome. The present work aimed to describe a simple, reproducible, and low-cost 3D in vitro culture method to generate bladder tumor spheroids using human cells from PDX mice. Cancer cells from PDX BL0293 and BL0808 models, previously established from advanced bladder cancer, were cultured in 96-well round-bottom ultra-low attachment (ULA) plates with 5% Matrigel and generated regular and round-shaped spheroids (roundness > 0.8) with a diameter larger than 400 μm and a hypoxic core (a feature related to drug resistance in solid tumors). The responses of the tumor spheroids to the antineoplastic drugs cisplatin, gemcitabine, and their combination were similar to tumor responses in in vivo studies with PDX BL0293 and BL0808 mice. Therefore, the in vitro 3D model using PDX tumor spheroids appears as a valuable tool that may predict the outcome of in vivo drug-screening assays and represents a low-cost strategy for such purpose.https://www.mdpi.com/2072-6694/12/5/13043D cell culturePDX modelstumor spheroidsbladder cellsultra-low attachment platesMatrigel |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robson Amaral Maike Zimmermann Ai-Hong Ma Hongyong Zhang Kamilla Swiech Chong-Xian Pan |
spellingShingle |
Robson Amaral Maike Zimmermann Ai-Hong Ma Hongyong Zhang Kamilla Swiech Chong-Xian Pan A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models Cancers 3D cell culture PDX models tumor spheroids bladder cells ultra-low attachment plates Matrigel |
author_facet |
Robson Amaral Maike Zimmermann Ai-Hong Ma Hongyong Zhang Kamilla Swiech Chong-Xian Pan |
author_sort |
Robson Amaral |
title |
A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models |
title_short |
A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models |
title_full |
A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models |
title_fullStr |
A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models |
title_full_unstemmed |
A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models |
title_sort |
simple three-dimensional in vitro culture mimicking the in vivo-like cell behavior of bladder patient-derived xenograft models |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-05-01 |
description |
Patient-derived xenograft (PDX) models allow for personalized drug selection and the identification of drug resistance mechanisms in cancer cells. However, PDX models present technical disadvantages, such as long engraftment time, low success rate, and high maintenance cost. On the other hand, tumor spheroids are emerging as an in vitro alternative model that can maintain the phenotype of cancer cells long enough to perform all assays and predict a patient’s outcome. The present work aimed to describe a simple, reproducible, and low-cost 3D in vitro culture method to generate bladder tumor spheroids using human cells from PDX mice. Cancer cells from PDX BL0293 and BL0808 models, previously established from advanced bladder cancer, were cultured in 96-well round-bottom ultra-low attachment (ULA) plates with 5% Matrigel and generated regular and round-shaped spheroids (roundness > 0.8) with a diameter larger than 400 μm and a hypoxic core (a feature related to drug resistance in solid tumors). The responses of the tumor spheroids to the antineoplastic drugs cisplatin, gemcitabine, and their combination were similar to tumor responses in in vivo studies with PDX BL0293 and BL0808 mice. Therefore, the in vitro 3D model using PDX tumor spheroids appears as a valuable tool that may predict the outcome of in vivo drug-screening assays and represents a low-cost strategy for such purpose. |
topic |
3D cell culture PDX models tumor spheroids bladder cells ultra-low attachment plates Matrigel |
url |
https://www.mdpi.com/2072-6694/12/5/1304 |
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