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Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples

Guillermo Bordanaba-Florit, Félix Royo, Oihane E. Albóniga, Aled Clayton, Juan Manuel Falcón-Pérez, Jason Webber Orcid Logo

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume: 1870, Issue: 6, Start page: 167229

Swansea University Author: Jason Webber Orcid Logo

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DOI (Published version): 10.1016/j.bbadis.2024.167229

Abstract

The prostate gland is a complex and heterogeneous organ composed of epithelium and stroma. Whilst many studies into prostate cancer focus on epithelium, the stroma is known to play a key role in disease with the emergence of a cancer-associated fibroblasts (CAF) phenotype associated upon disease pro...

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Published in: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
ISSN: 0925-4439
Published: Elsevier BV 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa67054
first_indexed 2024-07-09T14:45:42Z
last_indexed 2024-11-25T14:19:27Z
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spelling 2024-09-02T10:51:55.9435493 v2 67054 2024-07-09 Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples 25d1a26f9b8bb556bd9412080e40351d 0000-0003-4772-3014 Jason Webber Jason Webber true false 2024-07-09 MEDS The prostate gland is a complex and heterogeneous organ composed of epithelium and stroma. Whilst many studies into prostate cancer focus on epithelium, the stroma is known to play a key role in disease with the emergence of a cancer-associated fibroblasts (CAF) phenotype associated upon disease progression. In this work, we studied the metabolic rewiring of stromal fibroblasts following differentiation to a cancer-associated, myofibroblast-like, phenotype. We determined that CAFs were metabolically more active compared to normal fibroblasts. This corresponded with a heightened lipogenic metabolism, as both reservoir species and building block compounds. Interestingly, lipid metabolism affects mitochondria functioning yet the mechanisms of lipid-mediated functions are unclear. Data showing oxidised fatty acids and glutathione system are elevated in CAFs, compared to normal fibroblasts, strengthens the hypothesis that increased metabolic activity is related to mitochondrial activity. This manuscript describes mechanisms responsible for the altered metabolic flux and shows that prostate cancer-derived extracellular vesicles can increase basal respiration in normal fibroblasts, mirroring that of the disease-like phenotype. This indicates that extracellular vesicles derived from prostate cancer cells may drive an altered oxygen-dependent metabolism associated to mitochondria in CAFs. Journal Article Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1870 6 167229 Elsevier BV 0925-4439 Mass spectrometry; Prostate cancer; Metabolism; Extracellular vesicles; Human primary fibroblasts 1 8 2024 2024-08-01 10.1016/j.bbadis.2024.167229 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee The authors of this study were supported by funds from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 860303. European Union also funded this work with two Horizon grant agreements, no. 101079264 and no. 101095679 . The study was also supported from a Cancer Research Wales Programme Grant. The European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD) with the cost action STSM-BM1202 under grant number 190514-044080 financed a Short-Term Scientific Mission of J. W. 2024-09-02T10:51:55.9435493 2024-07-09T15:38:43.8294623 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Guillermo Bordanaba-Florit 1 Félix Royo 2 Oihane E. Albóniga 3 Aled Clayton 4 Juan Manuel Falcón-Pérez 5 Jason Webber 0000-0003-4772-3014 6 67054__31208__c7832f168f1e450eabebc3b781decb05.pdf 67054.VoR.pdf 2024-09-02T10:50:08.5113337 Output 5957090 application/pdf Version of Record true © 2024 The Authors. This is an open access article under the CC BY license. true eng http://creativecommons.org/licenses/by/4.0/
title Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
spellingShingle Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
Jason Webber
title_short Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
title_full Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
title_fullStr Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
title_full_unstemmed Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
title_sort Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
author_id_str_mv 25d1a26f9b8bb556bd9412080e40351d
author_id_fullname_str_mv 25d1a26f9b8bb556bd9412080e40351d_***_Jason Webber
author Jason Webber
author2 Guillermo Bordanaba-Florit
Félix Royo
Oihane E. Albóniga
Aled Clayton
Juan Manuel Falcón-Pérez
Jason Webber
format Journal article
container_title Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
container_volume 1870
container_issue 6
container_start_page 167229
publishDate 2024
institution Swansea University
issn 0925-4439
doi_str_mv 10.1016/j.bbadis.2024.167229
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description The prostate gland is a complex and heterogeneous organ composed of epithelium and stroma. Whilst many studies into prostate cancer focus on epithelium, the stroma is known to play a key role in disease with the emergence of a cancer-associated fibroblasts (CAF) phenotype associated upon disease progression. In this work, we studied the metabolic rewiring of stromal fibroblasts following differentiation to a cancer-associated, myofibroblast-like, phenotype. We determined that CAFs were metabolically more active compared to normal fibroblasts. This corresponded with a heightened lipogenic metabolism, as both reservoir species and building block compounds. Interestingly, lipid metabolism affects mitochondria functioning yet the mechanisms of lipid-mediated functions are unclear. Data showing oxidised fatty acids and glutathione system are elevated in CAFs, compared to normal fibroblasts, strengthens the hypothesis that increased metabolic activity is related to mitochondrial activity. This manuscript describes mechanisms responsible for the altered metabolic flux and shows that prostate cancer-derived extracellular vesicles can increase basal respiration in normal fibroblasts, mirroring that of the disease-like phenotype. This indicates that extracellular vesicles derived from prostate cancer cells may drive an altered oxygen-dependent metabolism associated to mitochondria in CAFs.
published_date 2024-08-01T08:32:39Z
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