The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells
Malignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, w...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/15/2/199 |
| _version_ | 1797298174922063872 |
|---|---|
| author | Stefania Oliveto Paolo Ritter Giorgia Deroma Annarita Miluzio Chiara Cordiglieri Mauro Roberto Benvenuti Luciano Mutti Manuela Teresa Raimondi Stefano Biffo |
| author_facet | Stefania Oliveto Paolo Ritter Giorgia Deroma Annarita Miluzio Chiara Cordiglieri Mauro Roberto Benvenuti Luciano Mutti Manuela Teresa Raimondi Stefano Biffo |
| author_sort | Stefania Oliveto |
| collection | DOAJ |
| description | Malignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, we analyzed the plasticity of gene expression of primary mesothelial cancer cells by comparing their properties on 2D versus 3D surfaces. First, we derived from primary human samples four independent primary cancer cells. Then, we used Nichoids, which are micro-engineered 3D substrates, as three-dimensional structures. Nichoids limit the dimension of adhering cells during expansion by counteracting cell migration between adjacent units of a substrate with their microarchitecture. Tumor cells grow effectively on Nichoids, where they show enhanced proliferation. We performed RNAseq analyses on all the samples and compared the gene expression pattern of Nichoid-grown tumor cells to that of cells grown in a 2D culture. The PCA analysis showed that 3D samples were more transcriptionally similar compared to the 2D ones. The 3D Nichoids induced a transcriptional remodeling that affected mainly genes involved in extracellular matrix assembly. Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells’ tensegrity or the mechanical stability of their structure. |
| first_indexed | 2024-03-07T22:32:05Z |
| format | Article |
| id | doaj.art-da07d5437ff04f12a2ccfba12b22cb2f |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-07T22:32:05Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-da07d5437ff04f12a2ccfba12b22cb2f2024-02-23T15:17:48ZengMDPI AGGenes2073-44252024-02-0115219910.3390/genes15020199The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma CellsStefania Oliveto0Paolo Ritter1Giorgia Deroma2Annarita Miluzio3Chiara Cordiglieri4Mauro Roberto Benvenuti5Luciano Mutti6Manuela Teresa Raimondi7Stefano Biffo8Department of Biosciences, University of Milan, 20133 Milan, ItalyNational Institute of Molecular Genetics, Fondazione Romeo ed Enrica Invernizzi, INGM, 20122 Milan, ItalyDepartment of Biosciences, University of Milan, 20133 Milan, ItalyNational Institute of Molecular Genetics, Fondazione Romeo ed Enrica Invernizzi, INGM, 20122 Milan, ItalyNational Institute of Molecular Genetics, Fondazione Romeo ed Enrica Invernizzi, INGM, 20122 Milan, ItalyThoracic Surgery Unit, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, Medical Oncology, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, ItalyDepartment of Applied Clinical Sciences and Biotechnology, DISCAB, Aquila University, 67100 L’ Aquila, ItalyDepartment of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, 20133 Milano, ItalyDepartment of Biosciences, University of Milan, 20133 Milan, ItalyMalignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, we analyzed the plasticity of gene expression of primary mesothelial cancer cells by comparing their properties on 2D versus 3D surfaces. First, we derived from primary human samples four independent primary cancer cells. Then, we used Nichoids, which are micro-engineered 3D substrates, as three-dimensional structures. Nichoids limit the dimension of adhering cells during expansion by counteracting cell migration between adjacent units of a substrate with their microarchitecture. Tumor cells grow effectively on Nichoids, where they show enhanced proliferation. We performed RNAseq analyses on all the samples and compared the gene expression pattern of Nichoid-grown tumor cells to that of cells grown in a 2D culture. The PCA analysis showed that 3D samples were more transcriptionally similar compared to the 2D ones. The 3D Nichoids induced a transcriptional remodeling that affected mainly genes involved in extracellular matrix assembly. Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells’ tensegrity or the mechanical stability of their structure.https://www.mdpi.com/2073-4425/15/2/199NFATC1epithelioidorganoidsmalignant pleural mesotheliomaextracellular matrix |
| spellingShingle | Stefania Oliveto Paolo Ritter Giorgia Deroma Annarita Miluzio Chiara Cordiglieri Mauro Roberto Benvenuti Luciano Mutti Manuela Teresa Raimondi Stefano Biffo The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells Genes NFATC1 epithelioid organoids malignant pleural mesothelioma extracellular matrix |
| title | The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells |
| title_full | The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells |
| title_fullStr | The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells |
| title_full_unstemmed | The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells |
| title_short | The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells |
| title_sort | impact of 3d nichoids and matrix stiffness on primary malignant mesothelioma cells |
| topic | NFATC1 epithelioid organoids malignant pleural mesothelioma extracellular matrix |
| url | https://www.mdpi.com/2073-4425/15/2/199 |
| work_keys_str_mv | AT stefaniaoliveto theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT paoloritter theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT giorgiaderoma theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT annaritamiluzio theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT chiaracordiglieri theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT maurorobertobenvenuti theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT lucianomutti theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT manuelateresaraimondi theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT stefanobiffo theimpactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT stefaniaoliveto impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT paoloritter impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT giorgiaderoma impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT annaritamiluzio impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT chiaracordiglieri impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT maurorobertobenvenuti impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT lucianomutti impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT manuelateresaraimondi impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells AT stefanobiffo impactof3dnichoidsandmatrixstiffnessonprimarymalignantmesotheliomacells |