The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression

The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumor microenvironment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to...

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Bibliographic Details
Published in:Molecular & cellular proteomics 2021-01, Vol.20, p.100026-100026, Article 100026
Main Authors: Kawahara, Rebeca, Recuero, Saulo, Srougi, Miguel, Leite, Katia R.M., Thaysen-Andersen, Morten, Palmisano, Giuseppe
Format: Article
Language:English
Subjects:
Disease Progression
Glycomics
Glycopeptides - metabolism
Glycoproteins - metabolism
glycoproteomics
Glycosylation
Humans
Male
Neoplasm Grading
Polysaccharides - metabolism
Prostate - metabolism
prostate cancer
Prostatic Hyperplasia - metabolism
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Proteome
Proteomics
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Summary:The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumor microenvironment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to map the protein-, cell-, and tumor grade–specific N- and O-glycosylation in surgically removed PCa tissues spanning five histological grades (n = 10/grade) and tissues from patients with benign prostatic hyperplasia (n = 5). Quantitative glycomics revealed PCa grade–specific alterations of the oligomannosidic-, paucimannosidic-, and branched sialylated complex-type N-glycans, and dynamic remodeling of the sialylated core 1- and core 2-type O-glycome. Deep quantitative glycoproteomics identified ∼7400 unique N-glycopeptides from 500 N-glycoproteins and ∼500 unique O-glycopeptides from nearly 200 O-glycoproteins. With reference to a recent Tissue and Blood Atlas, our data indicate that paucimannosidic glycans of the PCa tissues arise mainly from immune cell–derived glycoproteins. Furthermore, the grade-specific PCa glycosylation arises primarily from dynamics in the cellular makeup of the PCa tumor microenvironment across grades involving increased oligomannosylation of prostate-derived glycoproteins and decreased bisecting GlcNAcylation of N-glycans carried by the extracellular matrix proteins. Furthermore, elevated expression of several oligosaccharyltransferase subunits and enhanced N-glycoprotein site occupancy were observed associated with PCa progression. Finally, correlations between the protein-specific glycosylation and PCa progression were observed including increased site-specific core 2-type O-glycosylation of collagen VI. In conclusion, integrated glycomics and glycoproteomics have enabled new insight into the complexity and dynamics of the tissue glycoproteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms. [Display omitted] •Glycomics and glycoproteomics of PCa tissues during disease progression.•Cell-specific dynamics of pauci- and oligomannosylation during PCa progression.•Increased N-glycan branching and core 2-type O-glycosylation in ECM glycoproteins.•Increased N-site occupancy and oligosaccharyltransferase expression in PCa. Integrated glycomics and glycoproteomics with reference to the established Tissue Atlas were used to uncover the cell-, protein-, site-, and structure-speci
ISSN:1535-9476
1535-9484
DOI:10.1074/mcp.RA120.002320