title: Proteoglycans and their roles in brain cancer.
abstract: Glioblastoma, a malignant brain cancer, is characterized by abnormal activation of receptor tyrosine kinase signalling pathways and a poor prognosis. Extracellular proteoglycans, including heparan sulfate and chondroitin sulfate, play critical roles in the regulation of cell signalling and migration via interactions with extracellular ligands, growth factor receptors and extracellular matrix components, as well as intracellular enzymes and structural proteins. In cancer, proteoglycans help drive multiple oncogenic pathways in tumour cells and promote critical tumour-microenvironment interactions. In the present review, we summarize the evidence for proteoglycan function in gliomagenesis and examine the expression of proteoglycans and their modifying enzymes in human glioblastoma using data obtained from The Cancer Genome Atlas (http://cancergenome.nih.gov/). Furthermore, we demonstrate an association between specific proteoglycan alterations and changes in receptor tyrosine kinases. Based on these data, we propose a model in which proteoglycans and their modifying enzymes promote receptor tyrosine kinase signalling and progression in glioblastoma, and we suggest that cancer-associated proteoglycans are promising biomarkers for disease and therapeutic targets.
authors.affiliation: Department of Neurological Surgery, UCSF, San Francisco, CA 94158, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wade
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Robinson
authors.forename: Jane R
authors.initials: JR
authors.lastname: Engler
authors.forename: Claudia
authors.initials: C
authors.lastname: Petritsch
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013429:Sulfatases; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D011509:Proteoglycans; C512478:EGFR protein, human; D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha; D015238:Sulfotransferases; C470792:SULF2 protein, human; D013429:Sulfatases