Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate
Glioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/10/1357 |
| _version_ | 1797552887631446016 |
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| author | Cyntanna C. Hawkins Tomader Ali Sasanka Ramanadham Anita B. Hjelmeland |
| author_facet | Cyntanna C. Hawkins Tomader Ali Sasanka Ramanadham Anita B. Hjelmeland |
| author_sort | Cyntanna C. Hawkins |
| collection | DOAJ |
| description | Glioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resection, radiation, and temozolomide (TMZ), a blood–brain barrier (BBB) penetrant chemotherapy. Radiation and TMZ cause sphingomyelinases (SMase) to hydrolyze sphingomyelins to generate ceramides, which induce apoptosis. However, cells can evade apoptosis by converting ceramides to sphingosine-1-phosphate (S1P). S1P has been implicated in a wide range of cancers including GBM. Upregulation of S1P has been linked to the proliferation and invasion of GBM and other cancers that display a propensity for brain metastasis. To mediate their biological effects, SMases and S1P modulate signaling via phospholipase C (PLC) and phospholipase D (PLD). In addition, both SMase and S1P may alter the integrity of the BBB leading to infiltration of tumor-promoting immune populations. SMase activity has been associated with tumor evasion of the immune system, while S1P creates a gradient for trafficking of innate and adaptive immune cells. This review will explore the role of sphingolipid metabolism and pharmacological interventions in GBM and metastatic brain tumors with a focus on SMase and S1P. |
| first_indexed | 2024-03-10T16:07:26Z |
| format | Article |
| id | doaj.art-3a595464e71d4edbb29a930078de41ac |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:07:26Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-3a595464e71d4edbb29a930078de41ac2023-11-20T14:47:05ZengMDPI AGBiomolecules2218-273X2020-09-011010135710.3390/biom10101357Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-PhosphateCyntanna C. Hawkins0Tomader Ali1Sasanka Ramanadham2Anita B. Hjelmeland3Department of Cell, Developmental, and Integrative Biology, University of Birmingham at Alabama, Birmingham, AL 35233, USAResearch Department, Imperial College London Diabetes Centre, Abu Dhabi P.O. Box 48338, UAEDepartment of Cell, Developmental, and Integrative Biology, University of Birmingham at Alabama, Birmingham, AL 35233, USADepartment of Cell, Developmental, and Integrative Biology, University of Birmingham at Alabama, Birmingham, AL 35233, USAGlioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resection, radiation, and temozolomide (TMZ), a blood–brain barrier (BBB) penetrant chemotherapy. Radiation and TMZ cause sphingomyelinases (SMase) to hydrolyze sphingomyelins to generate ceramides, which induce apoptosis. However, cells can evade apoptosis by converting ceramides to sphingosine-1-phosphate (S1P). S1P has been implicated in a wide range of cancers including GBM. Upregulation of S1P has been linked to the proliferation and invasion of GBM and other cancers that display a propensity for brain metastasis. To mediate their biological effects, SMases and S1P modulate signaling via phospholipase C (PLC) and phospholipase D (PLD). In addition, both SMase and S1P may alter the integrity of the BBB leading to infiltration of tumor-promoting immune populations. SMase activity has been associated with tumor evasion of the immune system, while S1P creates a gradient for trafficking of innate and adaptive immune cells. This review will explore the role of sphingolipid metabolism and pharmacological interventions in GBM and metastatic brain tumors with a focus on SMase and S1P.https://www.mdpi.com/2218-273X/10/10/1357glioblastomasphingolipidsphingosine-1-phosphatesphingomyelinasesphingomyelinmetastasis |
| spellingShingle | Cyntanna C. Hawkins Tomader Ali Sasanka Ramanadham Anita B. Hjelmeland Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate Biomolecules glioblastoma sphingolipid sphingosine-1-phosphate sphingomyelinase sphingomyelin metastasis |
| title | Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate |
| title_full | Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate |
| title_fullStr | Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate |
| title_full_unstemmed | Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate |
| title_short | Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate |
| title_sort | sphingolipid metabolism in glioblastoma and metastatic brain tumors a review of sphingomyelinases and sphingosine 1 phosphate |
| topic | glioblastoma sphingolipid sphingosine-1-phosphate sphingomyelinase sphingomyelin metastasis |
| url | https://www.mdpi.com/2218-273X/10/10/1357 |
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