A Novel Truncated Form of Nephronectin Is Present in Small Extracellular Vesicles Isolated from 66cl4 Cells

Extracellular vesicles are emerging as biomarkers in breast cancer. Our recent report suggested that an intracellular granular staining pattern of the extracellular matrix protein nephronectin (NPNT) in breast tumor sections correlated with a poor prognosis. Furthermore, the results showed that NPNT...

Full description

Saved in:
Bibliographic Details
Published in:Journal of proteome research 2019-03, Vol.18 (3), p.1237-1247
Main Authors: Toraskar, Jimita, Magnussen, Synnøve N, Hagen, Lars, Sharma, Animesh, Hoang, Linh, Bjørkøy, Geir, Svineng, Gunbjørg, Steigedal, Tonje S
Format: Article
Language:English
Subjects:
Animals
Biomarkers, Tumor - genetics
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Disease Models, Animal
Extracellular Matrix Proteins - genetics
Extracellular Vesicles - genetics
Extracellular Vesicles - pathology
Female
Gene Expression Regulation, Neoplastic - genetics
Glycosylation
Humans
Medical disciplines: 700
Medisinske Fag: 700
Mice
Protein Isoforms - genetics
Proteomics
VDP
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Extracellular vesicles are emerging as biomarkers in breast cancer. Our recent report suggested that an intracellular granular staining pattern of the extracellular matrix protein nephronectin (NPNT) in breast tumor sections correlated with a poor prognosis. Furthermore, the results showed that NPNT is localized in extracellular vesicles derived from mouse breast cancer cells. In this study, we performed proteomic analysis that revealed that several proteins, including tumor-promoting molecules, are differentially expressed in the cargo of small extracellular vesicles (sEVs) derived from NPNT-expressing mouse breast cancer cells. We also identified three different forms of NPNT at 80, 60, and 20 kDa. We report that the native form of NPNT at 60 kDa becomes further glycosylated and is detected as the 80 kDa NPNT, which may be processed by matrix metalloproteinases to a shorter form of around 20 kDa, which has not previously been described. Although both 80 and 20 kDa NPNT are detected in sEVs derived from breast cancer cells, the 20 kDa form of NPNT is concentrated in sEVs. In summary, we show that a novel truncated form of NPNT is found in sEVs derived from breast cancer cells.
ISSN:1535-3893
1535-3907
1535-3907
DOI:10.1021/acs.jproteome.8b00859