Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate
Abstract
:1. Introduction
2. Sphingomyelinases (SMases)
2.1. Glioblastoma (GBM)
2.2. Metastatic Cancers
3. Sphingosine-1-Phosphate (S1P)
3.1. Glioblastoma (GBM)
3.2. Metastatic Cancers
S1PR | Cancer Type | Alteration | Phenotype | Study |
---|---|---|---|---|
S1PR1 | GBM | Absence | Increased proliferation | Yoshida et al., 2010 [81] |
GBM | Presence | Increased proliferation | Young et al., 2007 [82] | |
Breast cancer | Decrease | Decreased metastasis | Nagahashi et al., 2018 [97] | |
Solid tumors | Decrease | Decreased migration | Liu et al., 2015 [102] | |
S1PR2 | GBM | Absence | Increased migration | Lepley et al., 2005 [83]; Malchinkkuu et al., 2008 [84] |
Melanoma | Decrease | Increased migration/invasion | Arikawa et al., 2003 [103] | |
S1PR3 | GBM | Presence | Increased proliferation | Young et al., 2007 [82] |
TNBC | Presence | Increased metastasis | Wang et al., 2018 [96] | |
Breast cancer | Decrease | Decreased migration | Filipenko et al., 2016 [100] | |
NSCLC | Decrease | Decreased metastasis | Zhao et al., 2016 [99] | |
S1PR4 | Breast cancer | Presence | Decreased survival | Ohotski et al., 2012 [104] |
S1PR5 | GBM | Presence | Increased proliferation | Young et al., 2007 [82] |
4. Phospholipase-Mediated Signaling
4.1. Glioblastoma (GBM)
4.2. Metastatic Cancers
5. Blood–Brain Barrier Integrity
6. Immune Trafficking
6.1. Adaptive Immunity
6.2. Innate Immunity
7. Altering Sphingolipid Metabolism for Therapeutic Intervention
7.1. Glioblastoma
7.2. Metastatic Cancers
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer Type | NCT Number | Dates | Drug Name | Primary Target | Phase | Results | FDA Approval? |
---|---|---|---|---|---|---|---|
GBM | NCT02490930 | July 2015–September 2017 | Fingolimod | S1PR1 antagonist | Early Phase 1 | Not Published | Yes |
Recurrent Glioma | NCT00006080 | September 2000–September 2004 | Fenretinide (Single Agent) | Ceramide | Phase 2 | Ineffective at the doses given | Yes |
Recurrent GBM | NCT00075491 | December 2003–March 2005 | Fenretinide (Combination treatment) | Ceramide | Phase 2 | Not Published due to termination | Yes |
Advanced solid tumors | NCT01488513 | August 2014–August 2015 | ABC294640 | SK inhibitor | Phase 1 | Tolerated up to 500mg bid | No |
Advanced solid tumors | NCT02834611 | March 2017–August 2019 | Ceramide NanoLiposome | Ceramide | Phase 1 | Not Published | No |
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Hawkins, C.C.; Ali, T.; Ramanadham, S.; Hjelmeland, A.B. Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate. Biomolecules 2020, 10, 1357. https://doi.org/10.3390/biom10101357
Hawkins CC, Ali T, Ramanadham S, Hjelmeland AB. Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate. Biomolecules. 2020; 10(10):1357. https://doi.org/10.3390/biom10101357
Chicago/Turabian StyleHawkins, Cyntanna C., Tomader Ali, Sasanka Ramanadham, and Anita B. Hjelmeland. 2020. "Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate" Biomolecules 10, no. 10: 1357. https://doi.org/10.3390/biom10101357