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Proteoglycans in prostate cancer

Nature Reviews Urology volume 9, pages 196–206 (2012)Cite this article

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Abstract

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.

Key Points

  • Proteoglycans are a family of complex macromolecules whose structure comprises a unique core protein substituted with structurally diverse carbohydrate chains termed glycosaminoglycans

  • Both core proteins and glycosaminoglycans participate in interactions with other extracellular matrix proteins, growth factors and chemokines to regulate cell functions

  • Individual proteoglycan species might have opposing roles in regulating cell growth, adhesion, migration and apoptosis

  • The proteoglycan composition of a tissue is the sum of synthetic and degradative activities of multiple cell types and will change in the unstable microenvironment of a developing tumor

  • Proteoglycan fine structure, particularly pattern of glycosaminoglycan sulfation is important in mediating their function; degradative enzymes in a developing tumor might modify that structure and thus alter function

  • In prostate cancer, versican and perlecan promote tumor progression, whereas decorin and betaglycan are tumor suppressors; syndecan-1 might have a dual role as an antagonist and agonist depending on disease stage and enzymatic conditions

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Figure 1: Proteoglycan groups based on the sites with which they associate.
Figure 2: Structural relationship of the four isoforms of versican.
Figure 3: Structural organization of the small leucine-rich proteoglycans.
Figure 4: Structural organization of perlecan.
Figure 5: Structural organization of syndecan-1.

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  1. Department of Pathology, Tumor Biology Section and Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, 27157, NC, USA

    Iris J. Edwards

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Edwards, I. Proteoglycans in prostate cancer. Nat Rev Urol 9, 196–206 (2012). https://doi.org/10.1038/nrurol.2012.19

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