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The Role and Function of Sphingolipids in Glioblastoma Multiforme

  • Loubna Abdel Hadi
  • Clara Di Vito
  • Giovanni Marfia
  • Stefania Elena Navone
  • Rolando Campanella
  • Laura RiboniEmail author
Chapter
  • 612 Downloads

Abstract

Aberrations in sphingolipid metabolism and thus levels have been implicated in promoting the aggressiveness of glioblastoma multiforme, one of the most lethal cancers in humans. A major player is sphingosine-1-phosphate, that pressures GBM cells to exhibit its hallmarks, leading to increased proliferation, invasiveness, stemness, angiogenesis and death resistance, this indicating a fine balance and interplay between S1P function and this malignancy. To the opposite GBM are organized to maintain low their ceramide and sphingomyelin levels, which in turn lead to a loss of growth control and to a gain of death resistance. While the mechanisms of these alterations are emerging, the sphingolipid signaling pathway has been implicated in controlling GBM action and mass, and in mediating the link of malignancy. Here we describe and discuss the current understanding on how GBM cells arm themselves with the abilities of manipulating sphingolipids, especially sphingosine-1-phosphate and ceramide, and how these alterations, through differential interactions, regulate different signaling pathways, and integrate GBM function and mass, thus providing molecular cues for GBM properties and progression. It is a future challenge unrevealing how the multiforme features of sphingolipid signaling could be effectively manipulated as strategies to optimize the efficacy and selectivity of future therapies for GBM.

Keywords

Glioblastoma multiforme Glioblastoma hallmarks Sphingolipids Sphingosine-1-phosphate Ceramide Sphingosine kinase Ceramide synthase Sphingomyelinase Glucosylceramide synthase Sphingomyelin synthase 

Abbreviations

2OHOA

2-Hydroxyoleic acid

A-ceramidase

Acid ceramidase

A-SMase

Acid sphingomyelinase

Bcl2L13

B-cell lymphoma 2-like 13

bFGF

Basic fibroblast growth factor

CD95L

CD95 ligand

CerS

Ceramide synthase

ECM

Extracellular matrix

EGF

Epidermal growth factor

ER

Endoplasmic reticulum

GlcCer

Glucosylceramide

GSCs

Glioblastoma stem-like cells

HIF

Hypoxia inducible factor

IL

Interleukin

N-SMase

Neutral sphingomyelinase

PAI-1

Plasminogen activator inhibitor-1

PAS

Plasminogen activator system

PERK

Protein kinase R-like endoplasmic reticulum kinase

PKCδ

Protein kinase C delta

PLD

Phospholipase D

PRKD2

Protein kinase D2

PTEN

Phosphatase and tensin homolog located on chromosome TEN

S1P

Sphingosine-1-phosphate

S1P1–5

Sphingosine-1-phosphate receptors 1–5

SPP2

Sphingosine-1-phosphate phosphatase 2

THC

Tetrahydrocannabinol

TMZ

Temozolomide

TNFα

Tumor necrosis factor α

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Loubna Abdel Hadi
    • 1
  • Clara Di Vito
    • 1
  • Giovanni Marfia
    • 2
  • Stefania Elena Navone
    • 2
  • Rolando Campanella
    • 3
  • Laura Riboni
    • 4
    Email author
  1. 1.Department of Medical Biotechnology and Translational Medicine, LITA-SegrateUniversity of MilanMilanItaly
  2. 2.Neurosurgery Unit, Laboratory of Experimental Neurosurgery and Cell Therapy, Fondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
  3. 3.Neurosurgical UnitSan Carlo Borromeo HospitalMilanItaly
  4. 4.Department of Medical Biotechnology and Translational Medicine, LITA-SegrateUniversity of MilanMilanItaly

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