Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy
Defining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/1/28 |
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| author | Gerardo Della Sala Consiglia Pacelli Francesca Agriesti Ilaria Laurenzana Francesco Tucci Mirko Tamma Nazzareno Capitanio Claudia Piccoli |
| author_facet | Gerardo Della Sala Consiglia Pacelli Francesca Agriesti Ilaria Laurenzana Francesco Tucci Mirko Tamma Nazzareno Capitanio Claudia Piccoli |
| author_sort | Gerardo Della Sala |
| collection | DOAJ |
| description | Defining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. To this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. The results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. All together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy. |
| first_indexed | 2024-03-10T01:52:47Z |
| format | Article |
| id | doaj.art-434bf07ca860415b86e321ab0a182d70 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T01:52:47Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-434bf07ca860415b86e321ab0a182d702023-11-23T13:02:31ZengMDPI AGBiomedicines2227-90592021-12-011012810.3390/biomedicines10010028Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer TherapyGerardo Della Sala0Consiglia Pacelli1Francesca Agriesti2Ilaria Laurenzana3Francesco Tucci4Mirko Tamma5Nazzareno Capitanio6Claudia Piccoli7Department of Marine Biotechnology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80125 Naples, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyLaboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDefining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. To this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. The results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. All together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy.https://www.mdpi.com/2227-9059/10/1/28oncometabolismcancer stem cellmetabolic therapymitochondriacisplatinosteosarcoma |
| spellingShingle | Gerardo Della Sala Consiglia Pacelli Francesca Agriesti Ilaria Laurenzana Francesco Tucci Mirko Tamma Nazzareno Capitanio Claudia Piccoli Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy Biomedicines oncometabolism cancer stem cell metabolic therapy mitochondria cisplatin osteosarcoma |
| title | Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy |
| title_full | Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy |
| title_fullStr | Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy |
| title_full_unstemmed | Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy |
| title_short | Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy |
| title_sort | unveiling metabolic vulnerability and plasticity of human osteosarcoma stem and differentiated cells to improve cancer therapy |
| topic | oncometabolism cancer stem cell metabolic therapy mitochondria cisplatin osteosarcoma |
| url | https://www.mdpi.com/2227-9059/10/1/28 |
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