Proteomic Characterization of SAS Cell-Derived Extracellular Vesicles in Relation to Both BPA and Neutron Irradiation Doses

Davide Perico; Ying Tong; Lichao Chen; Shoji Imamichi; Yu Sanada; Masamichi Ishiai; Minoru Suzuki; Mitsuko Masutani; Pierluigi Mauri

doi:10.3390/cells12121562

Proteomic Characterization of SAS Cell-Derived Extracellular Vesicles in Relation to Both BPA and Neutron Irradiation Doses

Cells. 2023 Jun 6;12(12):1562. doi: 10.3390/cells12121562.

Authors

Davide Perico¹, Ying Tong², Lichao Chen³, Shoji Imamichi^{2

3

4}, Yu Sanada⁴, Masamichi Ishiai³, Minoru Suzuki⁴, Mitsuko Masutani^{2

3}, Pierluigi Mauri^{1

5}

Affiliations

¹ Institute of Biomedical Technologies ITB-CNR, Via Fratelli Cervi 93, 20054 Segrate, Italy.
² Department of Molecular and Genomic Biomedicine, Center for Bioinformatics & Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
³ Central Radioisotope Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
⁴ Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
⁵ Institute of Life Sciences, Sant'Anna School of Advanced Studies, 56127 Pisa, Italy.

Abstract

Boron neutron capture therapy (BNCT) is a selective radiotherapy based on nuclear reaction that occurs when ¹⁰B atoms accumulated in cancer cells are irradiated by thermal neutrons, triggering a nuclear fission response leading to cell death. Despite its growing importance in cancer treatment, molecular characterization of its effects is still lacking. In this context, proteomics investigation can be useful to study BNCT effect and identify potential biomarkers. Hence, we performed proteomic analysis with nanoLC-MS/MS (liquid chromatography coupled to tandem mass spectrometry) on extracellular vesicles (EVs) isolated from SAS cultures treated or not with ¹⁰B-boronophenylalanine (BPA) and different doses of neutron irradiation, to study the cellular response related to both boron administration and neutrons action. Despite the interference of fetal bovine serum in the medium, we were able to stratify BPA- and BPA+ conditions and to identify EVs-derived proteins characterizing pathways potentially related to a BNCT effect such as apoptosis, DNA repair and inflammatory response. In particular, KLF11, SERPINA1 and SERPINF2 were up-regulated in BPA+, while POLE and SERPINC1 were up-regulated in BPA-. These results provide the first proteomic investigation of EVs treated with BNCT in different conditions and highlight the potentiality of proteomics for improving biomarkers identification and mechanisms understanding of BNCT.

Keywords: BNCT; BPA; LC-MS; extracellular vesicles; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Boron Compounds / therapeutic use
Boron Neutron Capture Therapy* / methods
Extracellular Vesicles*
Neutrons
Proteomics
Tandem Mass Spectrometry

Substances

Boron Compounds

Grants and funding

This work was supported by PON ELIXIR CNRBiOMICS (PIR01_00017) by the Italian Ministry for Universities and Research, Elixir Implementation Study Proteomics 2021–23 by the European Molecular Biology Laboratory—ELIXIR Consortium, and project (RF2019–12370396) by the Italian Ministry of Health to P.M. This work was also supported, in part, by JSPS Grant-in-Aid for Scientific Research, grant numbers 17K15814 (S.I.), 18H02693 (M.M.) and by research fund from Center Intelligence Care Systems, Inc. (M.M.).