|Kundu S, Forsberg-Nilsson K|
Glycosaminoglycans and Glioma Invasion
European Association of NeuroOncology Magazine 2014; 4 (2): 75-80
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Keywords: chondroitin sulphate, extracellular matrix, heparan sulphate, tumour invasion
There is a great need for novel therapies to target malignant glioma, a disease with an often dismal prognosis. One of the hallmarks of malignant glioma is its efficient invasion of the healthy brain parenchyma, which leads to rapidly recurrent disease upon surgical removal of the original tumour. To be able to establish new tumours at a distance from the original neoplasm, glioma cells must detach, migrate through the microenvironment, settle, and proliferate in their new location. This includes changing adhesive characteristics, breaking down extracellular matrix molecules (ECM), and perturbed growth factor signalling. Investigations of the glioma-specific ECM composition may therefore provide new insights into glioma infiltration. In this review, we focus on glycosaminoglycans, important components of the ECM that are long unbranched polysaccharides composed of repeating disaccharide units. We discuss the roles for hyaluronan, one of the major brain ECM molecules, and that of the proteoglycans, heparan sulphate proteoglycans (HSPG) and chondroitin sulphate proteoglycans (CSPG), in glioma biology. Heparan sulphate (HS) and chondroitin sulphate (CS) chains act together with a wide variety of bioactive molecules, and these interactions depend on the HS and CS sulphation patterns. HS and CS chain modifications are implicated not only in normal development and homoeostasis but they also play important roles in pathological conditions including cancer. Dysregulated glycosaminoglycans, their biosynthetic and degradation enzymes as well as the proteoglycan core proteins are known to affect several stages of tumour progression, angiogenesis, and metastasis. Finding the specific characteristics of tumour cells that confer this infiltrative capacity of glioma may offer new avenues for drug development.