Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 14

PMID 37446098

Authors

Montalbano Mauro

Perricone Ugo

Zachary Walton

Shirafkan Ali

Cristiana Rastellini

Luca Cicalese

Affiliations

Soon will be listed here.

Abstract

Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis.

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