The Complexity and Dynamics of the Tissue Glycoproteome Associated With Prostate Cancer Progression
| Autor: | Katia R. M. Leite, Saulo Recuero, Morten Thaysen-Andersen, Rebeca Kawahara, Giuseppe Palmisano, Miguel Srougi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics Special Issue: Glycoproteomics Glycosylation Proteome LTF lactotransferrin Prostatic Hyperplasia Biochemistry Analytical Chemistry glycomics Extracellular matrix chemistry.chemical_compound Prostate cancer Collagen VI BPH benign prostatic hyperplasia OST oligosaccharyltransferase FA formic acid chemistry.chemical_classification 0303 health sciences PSA prostate-specific antigen 030302 biochemistry & molecular biology Glycopeptides Prostate HCD higher-energy collision-induced dissociation prostate cancer PAP prostatic acid phosphatase Glycoproteomics ECM extracellular matrix GS Gleason score SPE solid phase extraction FWHM full width at half maximum Disease Progression PCa prostate cancer Biology Glycomics TFA trifluoroacetic acid 03 medical and health sciences COLÁGENO Polysaccharides medicine Humans glycoproteomics Molecular Biology PGC porous graphitized carbon 030304 developmental biology Glycoproteins Tumor microenvironment Research C2GNT core 2 β1 6-N-acetylglucosaminyltransferase Prostatic Neoplasms MS LAMA5 laminin subunit α-5 ACN acetonitrile medicine.disease Neu5Gc N-glycolylneuraminic acid GnT N-acetylglucosaminyltransferase chemistry Cancer research Neoplasm Grading Glycoprotein AGC automatic gain contro |
| Zdroj: | Molecular & Cellular Proteomics : MCP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1535-9484 |
| Popis: | 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. Graphical Abstract Highlights • 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. In Brief Integrated glycomics and glycoproteomics with reference to the established Tissue Atlas were used to uncover the cell-, protein-, site-, and structure-specific N- and O-glycosylation in prostate cancer tissues spanning five disease grades relatively to benign prostatic hyperplasia control tissues. Dynamic cell-specific changes in the paucimannosylation and oligomannosylation of known bone marrow– and prostate-derived glycoproteins, respectively, and increased N-glycan branching and core 2-type O-glycosylation of known extracellular matrix glycoproteins were found to be key changes associated with prostate cancer progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|