Inhibition of Glypican-3 Cleavage Results in Reduced Cell Proliferation in a Liver Cancer Cell Line.

Autor: Schepers EJ; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Emily.Schepers@cchmc.org., Lake C; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Glaser K; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Bondoc AJ; Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2023 Feb; Vol. 282, pp. 118-128. Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1016/j.jss.2022.09.011
Abstrakt: Introduction: Glypican-3 (GPC3) is a surface-bound proteoglycan overexpressed in pediatric liver cancer and utilized clinically as an immunohistochemical tumor marker. Furin is a proprotein convertase that is ubiquitously expressed and shown to modify GPC3 post-translationally. In experimental models of epithelial-based cancers, furin inhibition decreased tumor cell migration and proliferation representing a potential therapeutic target.
Methods: Using a synthetic furin inhibitor, we evaluated proliferation, migration, protein, and RNA expression in two liver cancer cell lines, HepG2 (GPC3-positive) and SKHep1 cells (GPC3-negative). Total furin protein and GPC3 protein expression were assessed to evaluate functional levels of furin.
Results: There was a reduction in HepG2 proliferation with addition of furin inhibitor at the 48-h timepoint, however there was an increase in HepG2 migration.
Conclusions: GPC3 cleavage in hepatoblastoma (HB) has a role in cell proliferation with therapeutic potential, however furin inhibition is not an appropriate target for GPC3-expressing HB due to increased migration which may enhance metastatic potential.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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