The complexity and diversity of proteoglycan structure means that they have a range of functions that regulate cell behavior.
Through multiple interactions of their core proteins and glycosaminoglycans with extracellular matrix proteins, growth factors and chemokines, proteoglycans affect cell signaling, motility, adhesion, growth and apoptosis. Progressive changes in proteoglycans occur in the tumor microenvironment, but neither the source nor consequences of those changes are well understood. Proteoglycans studied in prostate cancer include versican-a hyalectan regulator of cell adhesion and migration-and the small leucine-rich proteoglycans decorin, biglycan and lumican, which have roles in cell signaling and tissue organization. Studies support an inhibitory role in prostate cancer for decorin and lumican. Conversely, the basement membrane proteoglycan perlecan might be a tumor promoter through upregulation of sonic hedgehog signaling. Loss of the growth-inhibitory cell-surface proteoglycans syndecan-1 and betaglycan in early prostate cancer might facilitate progression, but syndecan-1 effects are pleiotropic and its renewed expression in advanced tumors might adversely affect outcome. Importantly, cellular changes and enzymatic activity in the developing tumor can alter proteoglycan composition and structure to modify their function. Emerging studies suggest that cancers, including those of the prostate, use these changes to promote their own survival, growth, and spread.
Written by:
Edwards IJ. Are you the author?
Department of Pathology, Tumor Biology Section and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.
Reference: Nat Rev Urol. 2012 Feb 21;9(4):196-206.
doi: 10.1038/nrurol.2012.19
PubMed Abstract
PMID: 22349653
