Skip to main content

ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Protein Biochemistry for Basic and Applied Sciences
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1359956

Expression of calpastatin hcast 3-25 and activity of the calpain/calpastatin system in human glioblastoma stem cells: possible involvement of hcast 3-25 in cell differentiation

Provisionally accepted
Sonia Spinelli Sonia Spinelli 1Federica Barbieri Federica Barbieri 2Monica Averna Monica Averna 3Tullio Florio Tullio Florio 2,4Marco Pedrazzi Marco Pedrazzi 3Beatrice S. Tremonti Beatrice S. Tremonti 2Michela Capraro Michela Capraro 3Roberta De Tullio Roberta De Tullio 3*
  • 1 Laboratory of Molecular Nephrology, Giannina Gaslini Institute (IRCCS), Genoa, Liguria, Italy
  • 2 Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genoa, Genova, Italy
  • 3 Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy
  • 4 San Martino Hospital (IRCCS), Genova, Liguria, Italy

The final, formatted version of the article will be published soon.

    Glioblastoma (GBM) is the most malignant brain tumor, characterized by cell heterogeneity comprising stem cells (GSCs) responsible for aggressiveness. The calpain/calpastatin (calp/cast) proteolytic system is involved in critical physiological processes and cancer progression. In this work we showed the expression profile of hcast 3-25 (a Type III calpastatin variant devoid of inhibitory units) and the members of the system in several patient-derived GSCs exploring the relationship between hcast 3-25 and activation/activity of calpains. Each GSC shows a peculiar calp/cast mRNA and protein expression pattern, and hcast 3-25 is the least expressed.Differentiation promotes upregulation of all the calp/cast system components except hcast 3-25 mRNA, which increased or decreased depending on individual GSC culture. Transfection of hcast 3-25-V5 into two selected GSCs indicated that hcast 3-25 effectively associates with calpains, supporting the digestion of selected calpain targets. Hcast 3-25 possibly affects the stem state promoting a differentiated, less aggressive phenotype.

    Keywords: hcast 3-25, calpastatin, Calpain, Glioblastoma stem cell, differentiation

    Received: 22 Dec 2023; Accepted: 03 Jul 2024.

    Copyright: © 2024 Spinelli, Barbieri, Averna, Florio, Pedrazzi, Tremonti, Capraro and De Tullio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Roberta De Tullio, Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.