Chondroitin Sulphate Proteoglycans in the Tumour Microenvironment

Abstract

Proteoglycans are macromolecules that are essential for the development of cells, human diseases and malignancies. In particular, chondroitin sulphate proteoglycans (CSPGs) accumulate in tumour stroma and play a key role in tumour growth and invasion by driving multiple oncogenic pathways in tumour cells and promoting crucial interactions in the tumour microenvironment (TME). These pathways involve receptor tyrosine kinase (RTK) signalling via the mitogen-activated protein kinase (MAPK) cascade and integrin signalling via the activation of focal adhesion kinase (FAK), which sustains the activation of extracellular signal-regulated kinases 1/2 (ERK1/2). Human CSPG4 is a type I transmembrane protein that is associated with the growth and progression of human brain tumours. It regulates cell signalling and migration by interacting with components of the extracellular matrix, extracellular ligands, growth factor receptors, intracellular enzymes and structural proteins. Its overexpression by tumour cells, perivascular cells and precursor/progenitor cells in gliomas suggests that it plays a role in their origin, progression and neo-angiogenesis and its aberrant expression in tumour cells may be a promising biomarker to monitor malignant progression and patient survival. The aim of this chapter is to review and discuss the role of CSPG4 in the TME of human gliomas, including its potential as a druggable therapeutic target.