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

Authors
  • Kawahara, Rebeca1
  • Recuero, Saulo2
  • Srougi, Miguel2
  • Leite, Katia R M2
  • Thaysen-Andersen, Morten3
  • Palmisano, Giuseppe4
  • 1 Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, USP, São Paulo, Brazil; Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, NSW, Australia. , (Australia)
  • 2 Laboratório de Investigação Médica da Disciplina de Urologia da Faculdade de Medicina da USP, São Paulo, Brazil. , (Brazil)
  • 3 Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia; Biomolecular Discovery Research Centre, Macquarie University, Sydney, NSW, Australia. Electronic address: [email protected] , (Australia)
  • 4 Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, USP, São Paulo, Brazil. Electronic address: [email protected] , (Brazil)
Type
Published Article
Journal
Molecular & Cellular Proteomics
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Jan 05, 2021
Volume
20
Pages
100026–100026
Identifiers
DOI: 10.1074/mcp.RA120.002320
PMID: 33127837
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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