Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy
The biology of cancer stem cells (CSCs) of pediatric cancers, such as hepatoblastoma, is sparsely explored. This is mainly due to the very immature nature of these tumors, which complicates the distinction of CSCs from the other tumor cells. Previously, we identified a CSC population in hepatoblasto...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5825 |
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| author | Mieun Lee-Theilen Delaine D. Fadini Julia R. Hadhoud Fleur van Dongen Gabriela Kroll Udo Rolle Henning C. Fiegel |
| author_facet | Mieun Lee-Theilen Delaine D. Fadini Julia R. Hadhoud Fleur van Dongen Gabriela Kroll Udo Rolle Henning C. Fiegel |
| author_sort | Mieun Lee-Theilen |
| collection | DOAJ |
| description | The biology of cancer stem cells (CSCs) of pediatric cancers, such as hepatoblastoma, is sparsely explored. This is mainly due to the very immature nature of these tumors, which complicates the distinction of CSCs from the other tumor cells. Previously, we identified a CSC population in hepatoblastoma cell lines expressing the CSC markers CD34 and CD90, cell surface Vimentin (csVimentin) and binding of OV-6. In this study, we detected the co-expression of the immune escape factor PD-L1 in the CSC population, whereas the other tumor cells remained negative. FACS data revealed that non-CSCs give rise to CSCs, reflecting plasticity of CSCs and non-CSCs in hepatoblastoma as seen in other tumors. When we treated cells with cisplatin and decitabine, a new CD34<sup>+/low</sup>OV-6<sup>low</sup>CD90<sup>+</sup> population emerged that lacked csVimentin and PD-L1 expression. Expression analyses showed that this new CSC subset shared similar pluripotency and EMT features with the already-known CSCs. FACS results further revealed that this subset is also generated from non-CSCs. In conclusion, we showed that hepatoblastoma CSCs express PD-L1 and that the biology of hepatoblastoma CSCs is of a plastic nature. Chemotherapeutic treatment leads to another CSC subset, which is highly chemoresistant and could be responsible for a poor prognosis after postoperative chemotherapy. |
| first_indexed | 2024-03-09T17:52:18Z |
| format | Article |
| id | doaj.art-6c2773319a444e109c2dec4a6e01411e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:18Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6c2773319a444e109c2dec4a6e01411e2023-11-24T10:39:17ZengMDPI AGCancers2072-66942022-11-011423582510.3390/cancers14235825Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon ChemotherapyMieun Lee-Theilen0Delaine D. Fadini1Julia R. Hadhoud2Fleur van Dongen3Gabriela Kroll4Udo Rolle5Henning C. Fiegel6Department of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, GermanyThe biology of cancer stem cells (CSCs) of pediatric cancers, such as hepatoblastoma, is sparsely explored. This is mainly due to the very immature nature of these tumors, which complicates the distinction of CSCs from the other tumor cells. Previously, we identified a CSC population in hepatoblastoma cell lines expressing the CSC markers CD34 and CD90, cell surface Vimentin (csVimentin) and binding of OV-6. In this study, we detected the co-expression of the immune escape factor PD-L1 in the CSC population, whereas the other tumor cells remained negative. FACS data revealed that non-CSCs give rise to CSCs, reflecting plasticity of CSCs and non-CSCs in hepatoblastoma as seen in other tumors. When we treated cells with cisplatin and decitabine, a new CD34<sup>+/low</sup>OV-6<sup>low</sup>CD90<sup>+</sup> population emerged that lacked csVimentin and PD-L1 expression. Expression analyses showed that this new CSC subset shared similar pluripotency and EMT features with the already-known CSCs. FACS results further revealed that this subset is also generated from non-CSCs. In conclusion, we showed that hepatoblastoma CSCs express PD-L1 and that the biology of hepatoblastoma CSCs is of a plastic nature. Chemotherapeutic treatment leads to another CSC subset, which is highly chemoresistant and could be responsible for a poor prognosis after postoperative chemotherapy.https://www.mdpi.com/2072-6694/14/23/5825solid pediatric cancerhepatoblastomacancer stem cellsCD34CD90csVimentin |
| spellingShingle | Mieun Lee-Theilen Delaine D. Fadini Julia R. Hadhoud Fleur van Dongen Gabriela Kroll Udo Rolle Henning C. Fiegel Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy Cancers solid pediatric cancer hepatoblastoma cancer stem cells CD34 CD90 csVimentin |
| title | Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy |
| title_full | Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy |
| title_fullStr | Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy |
| title_full_unstemmed | Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy |
| title_short | Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy |
| title_sort | hepatoblastoma cancer stem cells express pd l1 reveal plasticity and can emerge upon chemotherapy |
| topic | solid pediatric cancer hepatoblastoma cancer stem cells CD34 CD90 csVimentin |
| url | https://www.mdpi.com/2072-6694/14/23/5825 |
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