CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity
Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may ref...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2180 |
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| author | Andrea Kelemen Idan Carmi Iván Seress Péter Lőrincz Tamás Tölgyes Kristóf Dede Attila Bursics Edit I. Buzás Zoltán Wiener |
| author_facet | Andrea Kelemen Idan Carmi Iván Seress Péter Lőrincz Tamás Tölgyes Kristóf Dede Attila Bursics Edit I. Buzás Zoltán Wiener |
| author_sort | Andrea Kelemen |
| collection | DOAJ |
| description | Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44<sup>high</sup> cells produce more organoids with a higher proliferation intensity, as compared to CD44<sup>low</sup> cells. Interestingly, we detected an increased EV release by CD44<sup>high</sup> CRC cells. In addition, we found that the miRNA cargos of CD44<sup>high</sup> and CD44<sup>low</sup> cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44<sup>high</sup> cells induced the proliferation and activation of colon fibroblasts more strongly than CD44<sup>low</sup> cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation. |
| first_indexed | 2024-03-09T21:44:21Z |
| format | Article |
| id | doaj.art-be8759b7ff0549c1803d8ec19bef95f7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:44:21Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-be8759b7ff0549c1803d8ec19bef95f72023-11-23T20:21:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234218010.3390/ijms23042180CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release CapacityAndrea Kelemen0Idan Carmi1Iván Seress2Péter Lőrincz3Tamás Tölgyes4Kristóf Dede5Attila Bursics6Edit I. Buzás7Zoltán Wiener8Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, HungaryDepartment of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, HungaryDepartment of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, HungaryDepartment of Anatomy, Cell and Developmental Biology, Eötvös Loránd University of Sciences, H-1117 Budapest, HungaryUzsoki Hospital, H-1145 Budapest, HungaryUzsoki Hospital, H-1145 Budapest, HungaryUzsoki Hospital, H-1145 Budapest, HungaryDepartment of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, HungaryDepartment of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, HungaryExtracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44<sup>high</sup> cells produce more organoids with a higher proliferation intensity, as compared to CD44<sup>low</sup> cells. Interestingly, we detected an increased EV release by CD44<sup>high</sup> CRC cells. In addition, we found that the miRNA cargos of CD44<sup>high</sup> and CD44<sup>low</sup> cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44<sup>high</sup> cells induced the proliferation and activation of colon fibroblasts more strongly than CD44<sup>low</sup> cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.https://www.mdpi.com/1422-0067/23/4/2180exosomecancer stem cellorganoidcancer-associated fibroblastCD44CD133 |
| spellingShingle | Andrea Kelemen Idan Carmi Iván Seress Péter Lőrincz Tamás Tölgyes Kristóf Dede Attila Bursics Edit I. Buzás Zoltán Wiener CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity International Journal of Molecular Sciences exosome cancer stem cell organoid cancer-associated fibroblast CD44 CD133 |
| title | CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity |
| title_full | CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity |
| title_fullStr | CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity |
| title_full_unstemmed | CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity |
| title_short | CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity |
| title_sort | cd44 expression intensity marks colorectal cancer cell subpopulations with different extracellular vesicle release capacity |
| topic | exosome cancer stem cell organoid cancer-associated fibroblast CD44 CD133 |
| url | https://www.mdpi.com/1422-0067/23/4/2180 |
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