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Signaling Determinants of Glioma Cell Invasion

  • Aneta KwiatkowskaEmail author
  • Marc Symons
Chapter
  • 94 Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)

Abstract

Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. In addition, there is accumulating evidence that current therapeutic modalities, including anti-angiogenic therapy and radiotherapy, can enhance glioma invasiveness. Glioma cell invasion is stimulated by both autocrine and paracrine factors that act on a large array of cell surface-bound receptors. Key signaling elements that mediate receptor-initiated signaling in the regulation of glioblastoma invasion are Rho family GTPases, including Rac, RhoA and Cdc42. These GTPases regulate cell morphology and actin dynamics and stimulate cell squeezing through the narrow extracellular spaces that are typical of the brain parenchyma. Transient attachment of cells to the extracellular matrix is also necessary for glioblastoma cell invasion. Interactions with extracellular matrix components are mediated by integrins that initiate diverse intracellular signalling pathways. Key signaling elements stimulated by integrins include PI3K, Akt, mTOR and MAP kinases. In order to detach from the tumor mass, glioma cells secrete proteolytic enzymes that cleave cell surface adhesion molecules, including CD44 and L1. Key proteases produced by glioma cells include uPA, ADAMs and MMPs. Increased understanding of the molecular mechanisms that control glioma cell invasion has led to the identification of molecular targets for therapeutic intervention in this devastating disease.

Keywords

Glioblastoma Invasion Migration Rho GTPase PI3K Akt Protease 

Abbreviations

ATX

Autotaxin

BEHAB

Brain-enriched hyaluronic acid binding protein

DG

Dentate gyrus

DOCK180

Dedicator of cytokinesis 180

ECM

Extracellular matrix

ELMO1

Engulfment and cell motility-1

Gab1

Grb-2 associated binder-1

GAP

GTPase activating protein

GBM

Glioblastoma multiforme

GDI

Guanine nucleotide dissociation inhibitor

GEF

Guanine nucleotide exchange factor

HGG

High grade glioma

LGG

Low grade glioma

LPA

Lysophosphatidic acid

LPC

Lysophosphatidylcholine

MCP-1

Monocyte chemotactic protein-1

mDia

Mammalian homolog of Drosophila diaphanous

MMP

Matrix metalloproteinase

MT1-MMP

Membrane type metalloproteinase 1

NB

Non-neoplastic brain

NSC

Neural stem cell

PDGFR

Platelet-derived growth factor receptor

PI3K

Phosphatidylinositol 3-kinase

PDK1

PI3K-dependent kinase 1

PH

Pleckstrin homology domain

PTEN

Phosphatase and tensin homolog deleted on chromosome ten

p130Cas

Crk-associated substrate

ROCK

Rho-associated coiled-coil forming kinase

RTK

Receptor tyrosine kinase

SPARC

Secreted protein acidic and rich in cystein

SVZ

Subventricular zone

TAM

Tumor associated macrophage

TGFβ-1

Transforming growth factor-β-1

TIMP

Tissue inhibitor of metalloproteinases

TN-C

Tenascin-C

TSP-1

Thrombospondin-1

VEGF

Vascular endothelial growth factor

VEGFR-1

Vascular endothelial growth factor receptor-1

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Center for Oncology and Cell Biology, Laboratory for Brain Tumor Biology, Feinstein Institute for Medical ResearchManhassetUSA

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