Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
dc.contributor.author
dc.date.accessioned
2021-11-12T13:01:41Z
dc.date.available
2021-11-12T13:01:41Z
dc.date.issued
2021-10-22
dc.identifier.uri
dc.description.abstract
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
dc.description.sponsorship
This research was funded by Fundación Ramón Areces, Instituto de Salud Carlos III (PI1900372), Ministerio de Economía y Competitividad (DPI2016- 77156-R), and AstraZeneca
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
MDPI (Multidisciplinary Digital Publishing Institute)
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.3390/cancers13215320
dc.relation.ispartof
Cancers, 2021, vol. 13, núm. 21, p. 5320
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Attribution 4.0 International (CC BY 4.0)
dc.rights.uri
dc.source
Polonio Alcalá, Emma Rabionet Díaz, Marc Ruiz Martínez, Santiago Palomeras, Sònia Porta Balanyà, Rut Vásquez Dongo, Carmen Amalia Bosch Barrera, Joaquim Puig i Miquel, Teresa Ciurana, Quim de 2021 Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma Cancers 13 21 5320
dc.subject
dc.title
Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
034006
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
2072-6694