Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma
The identification of cancer stem cells (CSCs), which are implicated in tumor initiation, progression, therapy resistance, and relapse, is of great biological and clinical relevance. In glioblastoma (GBM), this is still a challenge, as no single marker is able to universally identify populations of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/828 |
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| author | Joana Vieira de Castro Céline S. Gonçalves Eduarda P. Martins Irene Miranda-Lorenzo Mariana T. Cerqueira Adhemar Longatto-Filho Afonso A. Pinto Rui L. Reis Nuno Sousa Christopher Heeschen Bruno M. Costa |
| author_facet | Joana Vieira de Castro Céline S. Gonçalves Eduarda P. Martins Irene Miranda-Lorenzo Mariana T. Cerqueira Adhemar Longatto-Filho Afonso A. Pinto Rui L. Reis Nuno Sousa Christopher Heeschen Bruno M. Costa |
| author_sort | Joana Vieira de Castro |
| collection | DOAJ |
| description | The identification of cancer stem cells (CSCs), which are implicated in tumor initiation, progression, therapy resistance, and relapse, is of great biological and clinical relevance. In glioblastoma (GBM), this is still a challenge, as no single marker is able to universally identify populations of GBM cancer stem cells (GSCs). Indeed, there is still controversy on whether biomarker-expressing cells fulfill the functional criteria of bona fide GSCs, despite being widely used. Here, we describe a novel subpopulation of autofluorescent (Fluo<sup>+</sup>) cells in GBM that bear all the functional characteristics of GSCs, including higher capacity to grow as neurospheres, long-term self-renewal ability, increased expression of stem cell markers, and enhanced in vivo tumorigenicity. Mechanistically, the autofluorescent phenotype is largely due to the intracellular accumulation of riboflavin, mediated by the ABC transporter ABCG2. In summary, our work identifies an intrinsic cellular autofluorescent phenotype enriched in GBM cells with functional stem cells features that can be used as a novel, simple and reliable biomarker to target these highly malignant tumors, with implications for GBM biological and clinical research. |
| first_indexed | 2024-03-09T00:50:12Z |
| format | Article |
| id | doaj.art-0db4e131446f4be8b626e1245af2ed22 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:50:12Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0db4e131446f4be8b626e1245af2ed222023-12-11T17:15:29ZengMDPI AGCancers2072-66942021-02-0113482810.3390/cancers13040828Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in GlioblastomaJoana Vieira de Castro0Céline S. Gonçalves1Eduarda P. Martins2Irene Miranda-Lorenzo3Mariana T. Cerqueira4Adhemar Longatto-Filho5Afonso A. Pinto6Rui L. Reis7Nuno Sousa8Christopher Heeschen9Bruno M. Costa10Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalStem Cells and Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, SpainICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalDepartment of Neurosurgery, Hospital de Braga, 4710-243 Braga, PortugalICVS/3B’s-PT Government Associate Laboratory, 4710-057/4805-017 Braga/Guimarães, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalStem Cells and Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, SpainLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, University of Minho, 4710-057 Braga, PortugalThe identification of cancer stem cells (CSCs), which are implicated in tumor initiation, progression, therapy resistance, and relapse, is of great biological and clinical relevance. In glioblastoma (GBM), this is still a challenge, as no single marker is able to universally identify populations of GBM cancer stem cells (GSCs). Indeed, there is still controversy on whether biomarker-expressing cells fulfill the functional criteria of bona fide GSCs, despite being widely used. Here, we describe a novel subpopulation of autofluorescent (Fluo<sup>+</sup>) cells in GBM that bear all the functional characteristics of GSCs, including higher capacity to grow as neurospheres, long-term self-renewal ability, increased expression of stem cell markers, and enhanced in vivo tumorigenicity. Mechanistically, the autofluorescent phenotype is largely due to the intracellular accumulation of riboflavin, mediated by the ABC transporter ABCG2. In summary, our work identifies an intrinsic cellular autofluorescent phenotype enriched in GBM cells with functional stem cells features that can be used as a novel, simple and reliable biomarker to target these highly malignant tumors, with implications for GBM biological and clinical research.https://www.mdpi.com/2072-6694/13/4/828cancer stem cellsglioblastoma stem cellsautofluorescencebiomarkervitamin B2 |
| spellingShingle | Joana Vieira de Castro Céline S. Gonçalves Eduarda P. Martins Irene Miranda-Lorenzo Mariana T. Cerqueira Adhemar Longatto-Filho Afonso A. Pinto Rui L. Reis Nuno Sousa Christopher Heeschen Bruno M. Costa Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma Cancers cancer stem cells glioblastoma stem cells autofluorescence biomarker vitamin B2 |
| title | Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma |
| title_full | Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma |
| title_fullStr | Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma |
| title_full_unstemmed | Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma |
| title_short | Intracellular Autofluorescence as a New Biomarker for Cancer Stem Cells in Glioblastoma |
| title_sort | intracellular autofluorescence as a new biomarker for cancer stem cells in glioblastoma |
| topic | cancer stem cells glioblastoma stem cells autofluorescence biomarker vitamin B2 |
| url | https://www.mdpi.com/2072-6694/13/4/828 |
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