Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate.
Cyntanna C HawkinsTomader AliSasanka RamanadhamAnita B HjelmelandPublished in: Biomolecules (2020)
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.
Keyphrases
- chronic pain
- blood brain barrier
- cell cycle arrest
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- cerebral ischemia
- pi k akt
- oxidative stress
- squamous cell carcinoma
- small cell lung cancer
- healthcare
- immune response
- signaling pathway
- heart rate
- free survival
- poor prognosis
- cell proliferation
- white matter
- physical activity
- quality improvement
- young adults
- resting state
- quantum dots
- resistance training
- affordable care act
- health insurance
- childhood cancer