Glycosaminoglycans and Glioma Invasion

• There is a great need for novel therapiesto target malignant glioma, a disease withan often dismal prognosis. One of the hallmarksof malignant glioma is its effi cient invasion of thehealthy brain parenchyma, which leads to rapidlyrecurrent disease upon surgical removal of theoriginal tumour. To be able to establish new tumoursat a distance from the original neoplasm,glioma cells must detach, migrate through themicroenvironment, settle, and proliferate in theirnew location. This includes changing adhesivecharacteristics, breaking down extracellular matrixmolecules (ECM), and perturbed growth factorsignalling. Investigations of the glioma-specificECM composition may therefore provide newinsights into glioma infi ltration. In this review, wefocus on glycosaminoglycans, important componentsof the ECM that are long unbranched polysaccharidescomposed of repeating disaccharideunits. We discuss the roles for hyaluronan, one ofthe major brain ECM molecules, and that of theproteoglycans, heparan sulphate proteoglycans(HSPG) and chondroitin sulphate proteoglycans(CSPG), in glioma biology. Heparan sulphate (HS)and chondroitin sulphate (CS) chains act togetherwith a wide variety of bioactive molecules, andthese interactions depend on the HS and CS sulphationpatterns. HS and CS chain modifi cationsare implicated not only in normal developmentand homoeostasis but they also play importantroles in pathological conditions including cancer.Dysregulated glycosaminoglycans, their biosyntheticand degradation enzymes as well as theproteoglycan core proteins are known to affectseveral stages of tumour progression, angiogenesis,and metastasis. Finding the specifi c characteristicsof tumour cells that confer this infi ltrativecapacity of glioma may offer new avenuesfor drug development.

Nyckelord

heparan sulphate

chondroitin sulphate

extracellular matrix

tumour invasion

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