A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening

Colorectal cancer (CRC) is the third most common malignancy and has recently moved up to the second leading cause of death among carcinomas. Prognosis, especially for advanced diseases or certain molecular subtypes of CRC, remains poor, which highlights the urgent need for better therapeutic strateg...

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Autores principales:	Yordan Sbirkov, Diana Molander, Clement Milet, Ilia Bodurov, Boyko Atanasov, Radoslav Penkov, Nikolay Belev, Nico Forraz, Colin McGuckin, Victoria Sarafian
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	3D bioprinting colorectal cancer drug testing cancer modeling chemotherapeutic screening Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/0db0c7a3fa2348dda588b1f25c687ba1
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spelling	oai:doaj.org-article:0db0c7a3fa2348dda588b1f25c687ba12021-11-18T16:38:45ZA Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening2296-418510.3389/fbioe.2021.755563https://doaj.org/article/0db0c7a3fa2348dda588b1f25c687ba12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.755563/fullhttps://doaj.org/toc/2296-4185Colorectal cancer (CRC) is the third most common malignancy and has recently moved up to the second leading cause of death among carcinomas. Prognosis, especially for advanced diseases or certain molecular subtypes of CRC, remains poor, which highlights the urgent need for better therapeutic strategies. However, currently, as little as 0.1% of all drugs make it from bench to bedside because of the inherently high false-positive and false-negative rates of current preclinical and clinical drug testing data. Therefore, the success of developing novel treatment agents lies in the introduction of improved preclinical disease models which resemble in vivo carcinomas closer, possess higher predictive properties, and offer opportunities for individualized therapies. Aiming to address these needs, we have established an affordable, flexible, and highly reproducible 3D bioprinted CRC model. The histological assessment of Caco-2 cells in 3D bioprints revealed the formation of glandular-like structures which show greater pathomorphological resemblance to tumors than monolayer cultures do. RNA expression profiles in 3D bioprinted cells were marked by upregulation of genes involved in cell adhesion, hypoxia, EGFR/KRAS signaling, and downregulation of cell cycle programs. Testing this 3D experimental platform with three of the most commonly used chemotherapeutics in CRC (5-fluoruracil, oxaliplatin, and irinotecan) revealed overall increased resistance compared to 2D cell cultures. Last, we demonstrate that our workflow can be successfully extended to primary CRC samples. Thereby, we describe a novel accessible platform for disease modeling and drug testing, which may present an innovative opportunity for personalized therapeutic screening.Yordan SbirkovYordan SbirkovDiana MolanderDiana MolanderClement MiletIlia BodurovBoyko AtanasovBoyko AtanasovRadoslav PenkovNikolay BelevNikolay BelevNikolay BelevNico ForrazColin McGuckinVictoria SarafianVictoria SarafianFrontiers Media S.A.article3D bioprintingcolorectal cancerdrug testingcancer modelingchemotherapeutic screeningBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D bioprinting colorectal cancer drug testing cancer modeling chemotherapeutic screening Biotechnology TP248.13-248.65
spellingShingle	3D bioprinting colorectal cancer drug testing cancer modeling chemotherapeutic screening Biotechnology TP248.13-248.65 Yordan Sbirkov Yordan Sbirkov Diana Molander Diana Molander Clement Milet Ilia Bodurov Boyko Atanasov Boyko Atanasov Radoslav Penkov Nikolay Belev Nikolay Belev Nikolay Belev Nico Forraz Colin McGuckin Victoria Sarafian Victoria Sarafian A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
description	Colorectal cancer (CRC) is the third most common malignancy and has recently moved up to the second leading cause of death among carcinomas. Prognosis, especially for advanced diseases or certain molecular subtypes of CRC, remains poor, which highlights the urgent need for better therapeutic strategies. However, currently, as little as 0.1% of all drugs make it from bench to bedside because of the inherently high false-positive and false-negative rates of current preclinical and clinical drug testing data. Therefore, the success of developing novel treatment agents lies in the introduction of improved preclinical disease models which resemble in vivo carcinomas closer, possess higher predictive properties, and offer opportunities for individualized therapies. Aiming to address these needs, we have established an affordable, flexible, and highly reproducible 3D bioprinted CRC model. The histological assessment of Caco-2 cells in 3D bioprints revealed the formation of glandular-like structures which show greater pathomorphological resemblance to tumors than monolayer cultures do. RNA expression profiles in 3D bioprinted cells were marked by upregulation of genes involved in cell adhesion, hypoxia, EGFR/KRAS signaling, and downregulation of cell cycle programs. Testing this 3D experimental platform with three of the most commonly used chemotherapeutics in CRC (5-fluoruracil, oxaliplatin, and irinotecan) revealed overall increased resistance compared to 2D cell cultures. Last, we demonstrate that our workflow can be successfully extended to primary CRC samples. Thereby, we describe a novel accessible platform for disease modeling and drug testing, which may present an innovative opportunity for personalized therapeutic screening.
format	article
author	Yordan Sbirkov Yordan Sbirkov Diana Molander Diana Molander Clement Milet Ilia Bodurov Boyko Atanasov Boyko Atanasov Radoslav Penkov Nikolay Belev Nikolay Belev Nikolay Belev Nico Forraz Colin McGuckin Victoria Sarafian Victoria Sarafian
author_facet	Yordan Sbirkov Yordan Sbirkov Diana Molander Diana Molander Clement Milet Ilia Bodurov Boyko Atanasov Boyko Atanasov Radoslav Penkov Nikolay Belev Nikolay Belev Nikolay Belev Nico Forraz Colin McGuckin Victoria Sarafian Victoria Sarafian
author_sort	Yordan Sbirkov
title	A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
title_short	A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
title_full	A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
title_fullStr	A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
title_full_unstemmed	A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening
title_sort	colorectal cancer 3d bioprinting workflow as a platform for disease modeling and chemotherapeutic screening
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0db0c7a3fa2348dda588b1f25c687ba1
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A Colorectal Cancer 3D Bioprinting Workflow as a Platform for Disease Modeling and Chemotherapeutic Screening

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