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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Kawahara, Rebeca [1, 2, 3] ; Recuero, Saulo [4] ; Srougi, Miguel [4] ; Leite, Katia R. M. [4] ; Thaysen-Andersen, Morten [1, 3] ; Palmisano, Giuseppe [2]
Total Authors: 6
Affiliation:
[1] Macquarie Univ, Dept Mol Sci, Sydney, NSW - Australia
[2] Univ Sao Paulo, Inst Ciencias Biorned, Dept Parasitol, USP, Sao Paulo - Brazil
[3] Macquarie Univ, Biomol Discovery Res Ctr, Sydney, NSW - Australia
[4] Fac Med USP, Lab Invest Med Disciplina Urol, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: MOLECULAR & CELLULAR PROTEOMICS; v. 20, 2021.
Web of Science Citations: 3
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 similar to 7400 unique N-glycopeptides from 500 N-glycoproteins and similar to 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 glyco-proteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms. (AU)

FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
Grantee:Giuseppe Palmisano
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
Grantee:Giuseppe Palmisano
Support type: Multi-user Equipment Program
FAPESP's process: 15/02866-0 - DISCOVERY AND VERIFICATION OF INTACT GLYCOPEPTIDES AS CANDIDATE PROSTATE CANCER BIOMARKERS USING MASS SPECTROMETRY-BASED PROTEOMICS APPROACHES
Grantee:Rebeca Kawahara Sakuma
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
Grantee:Giuseppe Palmisano
Support type: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 17/03010-8 - Site-specific characterization of N- and O-linked glycosylation in prostate cancer tissues as molecular signature for disease progression
Grantee:Rebeca Kawahara Sakuma
Support type: Scholarships abroad - Research Internship - Post-doctor