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Lysophosphatidic Acid Signalling Enhances Glioma Stem Cell Properties

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Lipidomics of Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Glioblastoma multiforme (GBM) is a heterogeneous and malignant brain tumour with poor survival. Current survival with maximal treatment is only 15 months from diagnosis. These aggressive tumours recur after initial therapy due to their infiltrative nature. GBM recurrence and heterogeneity may also be due to GSC. The EGFR pathway and its downstream PI3K signalling are often dysregulated in GBM and have been shown to be involved in cell proliferation, survival, and migration. Complex interactions within and between signalling pathways exist. Lysophosphatidic acid (LPA) signalling components have been shown to be dysregulated in GBM. LPA signalling has been reported to interact with EGFR/PI3K signalling and has been shown to stimulate migration and invasion. Interactions between LPA and PI3K signalling may help explain treatment resistance to PI3K inhibitors and future studies investigating the combined use of EGFR/PI3K and LPA inhibitors may be promising.

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Abbreviations

ATX:

Autotaxin

BBB:

Blood–brain barrier

BTSC:

Brain tumour stem cell

CSC:

Cancer stem cell

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

GBM:

Glioblastoma multiforme

GFAP:

Glial fibrillary acidic protein

GSC:

Glioma stem cell

LPA:

Lysophosphatidic acid

LPAR:

LPA receptor

LPC:

Lysophosphatidylcholine

LPL:

Lysophospholipid

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloprotease

mTOR:

Mammalian target of rapamycin

NSC:

Neural stem cell

PI3K:

Phosphoinositide 3-kinase

PTEN:

Phosphatase tensin homologue

RMS:

Rostral migratory stream

S1P:

Sphingosine 1-phosphate

SVZ:

Subventricular zone

TMZ:

Temozolomide

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Authors and Affiliations

  1. University of Melbourne, Parkville, VIC, Australia

    Wayne Ng

  2. Department of Surgery, Centre for Medical Research, Royal Melbourne Hospital, Grattan Street, Parkville, VIC, 3050, Australia

    Wayne Ng

  3. Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia

    Wayne Ng

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  1. Wayne Ng
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Correspondence to Wayne Ng .

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  1. The University of Melbourne & Centre for Eye Research Australia, Melbourne, Victoria, Australia

    Alice Pébay

  2. The University of Melbourne & Centre for Eye Research Australia, Melbourne, Victoria, Australia

    Raymond C.B. Wong

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Ng, W. (2017). Lysophosphatidic Acid Signalling Enhances Glioma Stem Cell Properties. In: Pébay, A., Wong, R. (eds) Lipidomics of Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-49343-5_9

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