Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion
Ovarian cancer remains a deadly disease and its recurrence disease is due in part to the presence of disseminating ovarian cancer aggregates not removed by debulking surgery. During dissemination in a dynamic ascitic environment, the spheroid cells’ metabolism is characterized by low respiration and...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1399 |
| _version_ | 1797472504050089984 |
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| author | Stephanie L. E. Compton Joseph P. Grieco Benita Gollamudi Eric Bae Jennifer H. Van Mullekom Eva M. Schmelz |
| author_facet | Stephanie L. E. Compton Joseph P. Grieco Benita Gollamudi Eric Bae Jennifer H. Van Mullekom Eva M. Schmelz |
| author_sort | Stephanie L. E. Compton |
| collection | DOAJ |
| description | Ovarian cancer remains a deadly disease and its recurrence disease is due in part to the presence of disseminating ovarian cancer aggregates not removed by debulking surgery. During dissemination in a dynamic ascitic environment, the spheroid cells’ metabolism is characterized by low respiration and fragmented mitochondria, a metabolic phenotype that may not support secondary outgrowth after adhesion. Here, we investigated how adhesion affects cellular respiration and substrate utilization of spheroids mimicking early stages of secondary metastasis. Using different glucose and oxygen levels, we investigated cellular metabolism at early time points of adherence (24 h and less) comparing slow and fast-developing disease models. We found that adhesion over time showed changes in cellular energy metabolism and substrate utilization, with a switch in the utilization of mostly glutamine to glucose but no changes in fatty acid oxidation. Interestingly, low glucose levels had less of an impact on cellular metabolism than hypoxia. A resilience to culture conditions and the capacity to utilize a broader spectrum of substrates more efficiently distinguished the highly aggressive cells from the cells representing slow-developing disease, suggesting a flexible metabolism contributes to the stem-like properties. These results indicate that adhesion to secondary sites initiates a metabolic switch in the oxidation of substrates that could support outgrowth and successful metastasis. |
| first_indexed | 2024-03-09T20:02:40Z |
| format | Article |
| id | doaj.art-3131c8f26c2347e8b40dce6214a53fb5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:02:40Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3131c8f26c2347e8b40dce6214a53fb52023-11-24T00:40:24ZengMDPI AGCancers2072-66942022-03-01146139910.3390/cancers14061399Metabolic Reprogramming of Ovarian Cancer Spheroids during AdhesionStephanie L. E. Compton0Joseph P. Grieco1Benita Gollamudi2Eric Bae3Jennifer H. Van Mullekom4Eva M. Schmelz5Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24060, USATBMH, Fralin Biomedical Research Institute Virginia Tech, Roanoke, VA 24060, USASchool of Neuroscience, Virginia Tech, Blacksburg, VA 24061, USAStatistical Applications and Innovations Group, Department of Statistics, Virginia Tech, Blacksburg, VA 24061, USAStatistical Applications and Innovations Group, Department of Statistics, Virginia Tech, Blacksburg, VA 24061, USADepartment of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24060, USAOvarian cancer remains a deadly disease and its recurrence disease is due in part to the presence of disseminating ovarian cancer aggregates not removed by debulking surgery. During dissemination in a dynamic ascitic environment, the spheroid cells’ metabolism is characterized by low respiration and fragmented mitochondria, a metabolic phenotype that may not support secondary outgrowth after adhesion. Here, we investigated how adhesion affects cellular respiration and substrate utilization of spheroids mimicking early stages of secondary metastasis. Using different glucose and oxygen levels, we investigated cellular metabolism at early time points of adherence (24 h and less) comparing slow and fast-developing disease models. We found that adhesion over time showed changes in cellular energy metabolism and substrate utilization, with a switch in the utilization of mostly glutamine to glucose but no changes in fatty acid oxidation. Interestingly, low glucose levels had less of an impact on cellular metabolism than hypoxia. A resilience to culture conditions and the capacity to utilize a broader spectrum of substrates more efficiently distinguished the highly aggressive cells from the cells representing slow-developing disease, suggesting a flexible metabolism contributes to the stem-like properties. These results indicate that adhesion to secondary sites initiates a metabolic switch in the oxidation of substrates that could support outgrowth and successful metastasis.https://www.mdpi.com/2072-6694/14/6/1399ovarian cancermetabolismrespirationglucose uptakeglutaminespheroid |
| spellingShingle | Stephanie L. E. Compton Joseph P. Grieco Benita Gollamudi Eric Bae Jennifer H. Van Mullekom Eva M. Schmelz Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion Cancers ovarian cancer metabolism respiration glucose uptake glutamine spheroid |
| title | Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion |
| title_full | Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion |
| title_fullStr | Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion |
| title_full_unstemmed | Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion |
| title_short | Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion |
| title_sort | metabolic reprogramming of ovarian cancer spheroids during adhesion |
| topic | ovarian cancer metabolism respiration glucose uptake glutamine spheroid |
| url | https://www.mdpi.com/2072-6694/14/6/1399 |
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