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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5320 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:05:43Z |
| format | Article |
| id | doaj.art-958ccb821b5d4de8abd657d30fb2b573 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:05:43Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-958ccb821b5d4de8abd657d30fb2b5732023-11-22T20:33:31ZengMDPI AGCancers2072-66942021-10-011321532010.3390/cancers13215320Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung AdenocarcinomaEmma Polonio-Alcalá0Marc Rabionet1Santiago Ruiz-Martínez2Sònia Palomeras3Rut Porta4Carmen Vásquez-Dongo5Joaquim Bosch-Barrera6Teresa Puig7Joaquim Ciurana8Product, Process and Production Engineering Research Group (GREP), Department of Mechanical Engineering and Industrial Construction, University of Girona, 17003 Girona, SpainProduct, Process and Production Engineering Research Group (GREP), Department of Mechanical Engineering and Industrial Construction, University of Girona, 17003 Girona, SpainNew Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, 17003 Girona, SpainNew Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, 17003 Girona, SpainNew Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, 17003 Girona, SpainNew Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, 17003 Girona, SpainMedical Oncology Department, Catalan Institute of Oncology, 17007 Girona, SpainNew Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, 17003 Girona, SpainProduct, Process and Production Engineering Research Group (GREP), Department of Mechanical Engineering and Industrial Construction, University of Girona, 17003 Girona, SpainThe 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.https://www.mdpi.com/2072-6694/13/21/5320NSCLCcancer stem cells3D cell cultureelectrospinningCD133Vimentin |
| spellingShingle | 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 Cancers NSCLC cancer stem cells 3D cell culture electrospinning CD133 Vimentin |
| title | 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_short | 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 |
| topic | NSCLC cancer stem cells 3D cell culture electrospinning CD133 Vimentin |
| url | https://www.mdpi.com/2072-6694/13/21/5320 |
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