Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis....

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Autores principales:	Emma Polonio-Alcalá, Marc Rabionet, Santiago Ruiz-Martínez, Sònia Palomeras, Rut Porta, Carmen Vásquez-Dongo, Joaquim Bosch-Barrera, Teresa Puig, Joaquim Ciurana
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NSCLC cancer stem cells 3D cell culture electrospinning CD133 Vimentin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/958ccb821b5d4de8abd657d30fb2b573
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spelling	oai:doaj.org-article:958ccb821b5d4de8abd657d30fb2b5732021-11-11T15:28:16ZPolycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma10.3390/cancers132153202072-6694https://doaj.org/article/958ccb821b5d4de8abd657d30fb2b5732021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5320https://doaj.org/toc/2072-6694The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.Emma Polonio-AlcaláMarc RabionetSantiago Ruiz-MartínezSònia PalomerasRut PortaCarmen Vásquez-DongoJoaquim Bosch-BarreraTeresa PuigJoaquim CiuranaMDPI AGarticleNSCLCcancer stem cells3D cell cultureelectrospinningCD133VimentinNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5320, p 5320 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NSCLC cancer stem cells 3D cell culture electrospinning CD133 Vimentin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	NSCLC cancer stem cells 3D cell culture electrospinning CD133 Vimentin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Emma Polonio-Alcalá Marc Rabionet Santiago Ruiz-Martínez Sònia Palomeras Rut Porta Carmen Vásquez-Dongo Joaquim Bosch-Barrera Teresa Puig Joaquim Ciurana Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
description	The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.
format	article
author	Emma Polonio-Alcalá Marc Rabionet Santiago Ruiz-Martínez Sònia Palomeras Rut Porta Carmen Vásquez-Dongo Joaquim Bosch-Barrera Teresa Puig Joaquim Ciurana
author_facet	Emma Polonio-Alcalá Marc Rabionet Santiago Ruiz-Martínez Sònia Palomeras Rut Porta Carmen Vásquez-Dongo Joaquim Bosch-Barrera Teresa Puig Joaquim Ciurana
author_sort	Emma Polonio-Alcalá
title	Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
title_short	Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
title_full	Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
title_fullStr	Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
title_full_unstemmed	Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
title_sort	polycaprolactone electrospun scaffolds produce an enrichment of lung cancer stem cells in sensitive and resistant egfrm lung adenocarcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/958ccb821b5d4de8abd657d30fb2b573
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Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma

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