Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies
Osteosarcoma (OS) is a primary malignant bone tumor and OS metastases are mostly found in the lung. The limited understanding of the biology of metastatic processes in OS limits the ability for effective treatment. Alterations to the metabolome and its transformation during metastasis aids the under...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1371 |
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| author | Raphaela Fritsche-Guenther Yoann Gloaguen Marieluise Kirchner Philipp Mertins Per-Ulf Tunn Jennifer A. Kirwan |
| author_facet | Raphaela Fritsche-Guenther Yoann Gloaguen Marieluise Kirchner Philipp Mertins Per-Ulf Tunn Jennifer A. Kirwan |
| author_sort | Raphaela Fritsche-Guenther |
| collection | DOAJ |
| description | Osteosarcoma (OS) is a primary malignant bone tumor and OS metastases are mostly found in the lung. The limited understanding of the biology of metastatic processes in OS limits the ability for effective treatment. Alterations to the metabolome and its transformation during metastasis aids the understanding of the mechanism and provides information on treatment and prognosis. The current study intended to identify metabolic alterations during OS progression by using a targeted gas chromatography mass spectrometry approach. Using a female OS cell line model, malignant and metastatic cells increased their energy metabolism compared to benign OS cells. The metastatic cell line showed a faster metabolic flux compared to the malignant cell line, leading to reduced metabolite pools. However, inhibiting both glycolysis and glutaminolysis resulted in a reduced proliferation. In contrast, malignant but non-metastatic OS cells showed a resistance to glycolytic inhibition but a strong dependency on glutamine as an energy source. Our in vivo metabolic approach hinted at a potential sex-dependent metabolic alteration in OS patients with lung metastases (LM), although this will require validation with larger sample sizes. In line with the in vitro results, we found that female LM patients showed a decreased central carbon metabolism compared to metastases from male patients. |
| first_indexed | 2024-03-10T19:34:41Z |
| format | Article |
| id | doaj.art-658b036b0223464393f2168dec0cf4a9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:34:41Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-658b036b0223464393f2168dec0cf4a92023-11-20T01:50:54ZengMDPI AGCancers2072-66942020-05-01126137110.3390/cancers12061371Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source DependenciesRaphaela Fritsche-Guenther0Yoann Gloaguen1Marieluise Kirchner2Philipp Mertins3Per-Ulf Tunn4Jennifer A. Kirwan5Berlin Institute of Health Metabolomics Platform, Berlin Institute of Health (BIH), 13125 Berlin, GermanyBerlin Institute of Health Metabolomics Platform, Berlin Institute of Health (BIH), 13125 Berlin, GermanyMax Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, GermanyMax Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, GermanyDepartment of Orthopedic Oncology, Helios Clinic Berlin-Buch, 13125 Berlin, GermanyBerlin Institute of Health Metabolomics Platform, Berlin Institute of Health (BIH), 13125 Berlin, GermanyOsteosarcoma (OS) is a primary malignant bone tumor and OS metastases are mostly found in the lung. The limited understanding of the biology of metastatic processes in OS limits the ability for effective treatment. Alterations to the metabolome and its transformation during metastasis aids the understanding of the mechanism and provides information on treatment and prognosis. The current study intended to identify metabolic alterations during OS progression by using a targeted gas chromatography mass spectrometry approach. Using a female OS cell line model, malignant and metastatic cells increased their energy metabolism compared to benign OS cells. The metastatic cell line showed a faster metabolic flux compared to the malignant cell line, leading to reduced metabolite pools. However, inhibiting both glycolysis and glutaminolysis resulted in a reduced proliferation. In contrast, malignant but non-metastatic OS cells showed a resistance to glycolytic inhibition but a strong dependency on glutamine as an energy source. Our in vivo metabolic approach hinted at a potential sex-dependent metabolic alteration in OS patients with lung metastases (LM), although this will require validation with larger sample sizes. In line with the in vitro results, we found that female LM patients showed a decreased central carbon metabolism compared to metastases from male patients.https://www.mdpi.com/2072-6694/12/6/1371osteosarcomaGC-MSflux analysisglucoseglutaminesex and gender |
| spellingShingle | Raphaela Fritsche-Guenther Yoann Gloaguen Marieluise Kirchner Philipp Mertins Per-Ulf Tunn Jennifer A. Kirwan Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies Cancers osteosarcoma GC-MS flux analysis glucose glutamine sex and gender |
| title | Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies |
| title_full | Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies |
| title_fullStr | Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies |
| title_full_unstemmed | Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies |
| title_short | Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies |
| title_sort | progression dependent altered metabolism in osteosarcoma resulting in different nutrient source dependencies |
| topic | osteosarcoma GC-MS flux analysis glucose glutamine sex and gender |
| url | https://www.mdpi.com/2072-6694/12/6/1371 |
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