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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010466/ https://www.ncbi.nlm.nih.gov/pubmed/33127837 http://dx.doi.org/10.1074/mcp.RA120.002320 |
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author | Kawahara, Rebeca Recuero, Saulo Srougi, Miguel Leite, Katia R.M. Thaysen-Andersen, Morten Palmisano, Giuseppe |
author_facet | Kawahara, Rebeca Recuero, Saulo Srougi, Miguel Leite, Katia R.M. Thaysen-Andersen, Morten Palmisano, Giuseppe |
author_sort | Kawahara, Rebeca |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8010466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80104662021-04-02 The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression Kawahara, Rebeca Recuero, Saulo Srougi, Miguel Leite, Katia R.M. Thaysen-Andersen, Morten Palmisano, Giuseppe Mol Cell Proteomics Research 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. American Society for Biochemistry and Molecular Biology 2021-01-05 /pmc/articles/PMC8010466/ /pubmed/33127837 http://dx.doi.org/10.1074/mcp.RA120.002320 Text en © 2021 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Kawahara, Rebeca Recuero, Saulo Srougi, Miguel Leite, Katia R.M. Thaysen-Andersen, Morten Palmisano, Giuseppe The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title | The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title_full | The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title_fullStr | The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title_full_unstemmed | The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title_short | The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression |
title_sort | complexity and dynamics of the tissue glycoproteome associated with prostate cancer progression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010466/ https://www.ncbi.nlm.nih.gov/pubmed/33127837 http://dx.doi.org/10.1074/mcp.RA120.002320 |
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