Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models
Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options ar...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/399 |
| _version_ | 1797396429766918144 |
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| author | Marie-Anaïs Locquet Anne-Lise Dechaume Paul Berchard Lhorra Abbes Daniel Pissaloux Franck Tirode Inès Ramos Julie Bedoucha Julie Valantin Marie Karanian Raul Perret Olivier Gille Jean-Yves Blay Aurélie Dutour |
| author_facet | Marie-Anaïs Locquet Anne-Lise Dechaume Paul Berchard Lhorra Abbes Daniel Pissaloux Franck Tirode Inès Ramos Julie Bedoucha Julie Valantin Marie Karanian Raul Perret Olivier Gille Jean-Yves Blay Aurélie Dutour |
| author_sort | Marie-Anaïs Locquet |
| collection | DOAJ |
| description | Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models. |
| first_indexed | 2024-03-09T00:51:09Z |
| format | Article |
| id | doaj.art-0d8d3f204ead4803b379041bba79179e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:51:09Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0d8d3f204ead4803b379041bba79179e2023-12-11T17:10:07ZengMDPI AGCells2073-44092021-02-0110239910.3390/cells10020399Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular ModelsMarie-Anaïs Locquet0Anne-Lise Dechaume1Paul Berchard2Lhorra Abbes3Daniel Pissaloux4Franck Tirode5Inès Ramos6Julie Bedoucha7Julie Valantin8Marie Karanian9Raul Perret10Olivier Gille11Jean-Yves Blay12Aurélie Dutour13Team Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceDepartment of Biopathology, Centre Leon Berard, F-69008 Lyon, FranceTeam Genetics, Epigenetics and Biology of Sarcomas, Univ Lyon, Université Claude Bernard Lyon 1, INSERM1052, CNRS5286, Cancer Research Center of Lyon, Centre Leon Berard, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceResearch Pathology Platform, Department of Translational Research and Innovation, Centre Leon Berard, F-69008 Lyon, FranceDepartment of Biopathology, Centre Leon Berard, F-69008 Lyon, FranceDepartment of Biopathology, Institut Bergonié, F-33000 Bordeaux, FranceOrthopedic Spinal Surgery Unit 1, Bordeaux University Hospital, F-33000 Bordeaux, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceTeam Cell Death and Pediatric Cancer, Cancer Initiation and Tumor Cell Identity Department, INSERM1052, CNRS5286, Cancer Research Center of Lyon, F-69008 Lyon, FranceChordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models.https://www.mdpi.com/2073-4409/10/2/399chordoma3D modelshypoxiaradiotherapyaldehyde dehydrogenaseradioresistance |
| spellingShingle | Marie-Anaïs Locquet Anne-Lise Dechaume Paul Berchard Lhorra Abbes Daniel Pissaloux Franck Tirode Inès Ramos Julie Bedoucha Julie Valantin Marie Karanian Raul Perret Olivier Gille Jean-Yves Blay Aurélie Dutour Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models Cells chordoma 3D models hypoxia radiotherapy aldehyde dehydrogenase radioresistance |
| title | Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models |
| title_full | Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models |
| title_fullStr | Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models |
| title_full_unstemmed | Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models |
| title_short | Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models |
| title_sort | aldehyde dehydrogenase a therapeutic target in chordoma analysis in 3d cellular models |
| topic | chordoma 3D models hypoxia radiotherapy aldehyde dehydrogenase radioresistance |
| url | https://www.mdpi.com/2073-4409/10/2/399 |
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