Cargando…
Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression
BACKGROUND: Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear. METHODS: The content of PDI isoforms in 22 cancer cells lines was investigated using LC–MS/MS-based proteomi...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208212/ https://www.ncbi.nlm.nih.gov/pubmed/35725466 http://dx.doi.org/10.1186/s12935-022-02631-w |
_version_ | 1784729694878302208 |
---|---|
author | Kurpińska, Anna Suraj-Prażmowska, Joanna Stojak, Marta Jarosz, Joanna Mateuszuk, Łukasz Niedzielska-Andres, Ewa Smolik, Magdalena Wietrzyk, Joanna Kalvins, Ivars Walczak, Maria Chłopicki, Stefan |
author_facet | Kurpińska, Anna Suraj-Prażmowska, Joanna Stojak, Marta Jarosz, Joanna Mateuszuk, Łukasz Niedzielska-Andres, Ewa Smolik, Magdalena Wietrzyk, Joanna Kalvins, Ivars Walczak, Maria Chłopicki, Stefan |
author_sort | Kurpińska, Anna |
collection | PubMed |
description | BACKGROUND: Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear. METHODS: The content of PDI isoforms in 22 cancer cells lines was investigated using LC–MS/MS-based proteomic analysis. The effects of PDIA1, PDIA3 and PDIA17 inhibition on the proliferation, migration and adhesion of MCF-7 and MDA-MB-231 cells, identified as high and low PDIA17 expressing cells, respectively, were assessed using novel aromatic N-sulphonamides of aziridine-2-carboxylic acid derivatives as PDI inhibitors. RESULTS: PDIA1 and PDIA3 were the most abundant in cancer cell lysates and were also detected extracellularly in breast cancer cells (MDA-MB-231 and MCF-7). Some cancer cell lines (e.g., MCF-7, HT-29) showed upregulated expression of PDIA17, whereas in others (e.g., MDA-MB-231, 67NR), PDIA17 was not detected. The simultaneous inhibition of PDIA1 and PDIA3 showed similar anti-proliferative effects in MCF-7 and MDA-MB-231 breast cancer cells. However, the inhibition of PDIA1 and PDIA17 in the MCF-7 cell line resulted in more effective anti-adhesive and anti-proliferative effects. CONCLUSIONS: PDIA1 and PDIA3 represent major isoforms of multiple cancer cells, and their non-selective inhibition displays significant anti-proliferative effects irrespective of whether or not PDIA17 is present. The more pronounced anti-adhesive effects of PDI inhibition in hormone-sensitive MCF-7 cells featured by higher levels of PDIs when compared to triple-negative MDA-MB-231 cells suggests that targeting extracellular PDIA1 and PDIA3 with or without additional PDIA17 inhibition may represent a strategy for personalized anti-adhesive, anti-metastatic therapy in cancers with high PDI expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02631-w. |
format | Online Article Text |
id | pubmed-9208212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92082122022-06-21 Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression Kurpińska, Anna Suraj-Prażmowska, Joanna Stojak, Marta Jarosz, Joanna Mateuszuk, Łukasz Niedzielska-Andres, Ewa Smolik, Magdalena Wietrzyk, Joanna Kalvins, Ivars Walczak, Maria Chłopicki, Stefan Cancer Cell Int Research BACKGROUND: Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear. METHODS: The content of PDI isoforms in 22 cancer cells lines was investigated using LC–MS/MS-based proteomic analysis. The effects of PDIA1, PDIA3 and PDIA17 inhibition on the proliferation, migration and adhesion of MCF-7 and MDA-MB-231 cells, identified as high and low PDIA17 expressing cells, respectively, were assessed using novel aromatic N-sulphonamides of aziridine-2-carboxylic acid derivatives as PDI inhibitors. RESULTS: PDIA1 and PDIA3 were the most abundant in cancer cell lysates and were also detected extracellularly in breast cancer cells (MDA-MB-231 and MCF-7). Some cancer cell lines (e.g., MCF-7, HT-29) showed upregulated expression of PDIA17, whereas in others (e.g., MDA-MB-231, 67NR), PDIA17 was not detected. The simultaneous inhibition of PDIA1 and PDIA3 showed similar anti-proliferative effects in MCF-7 and MDA-MB-231 breast cancer cells. However, the inhibition of PDIA1 and PDIA17 in the MCF-7 cell line resulted in more effective anti-adhesive and anti-proliferative effects. CONCLUSIONS: PDIA1 and PDIA3 represent major isoforms of multiple cancer cells, and their non-selective inhibition displays significant anti-proliferative effects irrespective of whether or not PDIA17 is present. The more pronounced anti-adhesive effects of PDI inhibition in hormone-sensitive MCF-7 cells featured by higher levels of PDIs when compared to triple-negative MDA-MB-231 cells suggests that targeting extracellular PDIA1 and PDIA3 with or without additional PDIA17 inhibition may represent a strategy for personalized anti-adhesive, anti-metastatic therapy in cancers with high PDI expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02631-w. BioMed Central 2022-06-20 /pmc/articles/PMC9208212/ /pubmed/35725466 http://dx.doi.org/10.1186/s12935-022-02631-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kurpińska, Anna Suraj-Prażmowska, Joanna Stojak, Marta Jarosz, Joanna Mateuszuk, Łukasz Niedzielska-Andres, Ewa Smolik, Magdalena Wietrzyk, Joanna Kalvins, Ivars Walczak, Maria Chłopicki, Stefan Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title | Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title_full | Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title_fullStr | Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title_full_unstemmed | Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title_short | Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression |
title_sort | comparison of anti-cancer effects of novel protein disulphide isomerase (pdi) inhibitors in breast cancer cells characterized by high and low pdia17 expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208212/ https://www.ncbi.nlm.nih.gov/pubmed/35725466 http://dx.doi.org/10.1186/s12935-022-02631-w |
work_keys_str_mv | AT kurpinskaanna comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT surajprazmowskajoanna comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT stojakmarta comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT jaroszjoanna comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT mateuszukłukasz comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT niedzielskaandresewa comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT smolikmagdalena comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT wietrzykjoanna comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT kalvinsivars comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT walczakmaria comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression AT chłopickistefan comparisonofanticancereffectsofnovelproteindisulphideisomerasepdiinhibitorsinbreastcancercellscharacterizedbyhighandlowpdia17expression |