Journal article 156 views 17 downloads
Integration of proteomic and metabolomic analysis reveal distinct metabolic alterations of prostate cancer-associated fibroblasts compared to normal fibroblasts from patient's stroma samples
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume: 1870, Issue: 6, Start page: 167229
Swansea University Author:
Jason Webber
-
PDF | Version of Record
© 2024 The Authors. This is an open access article under the CC BY license.
Download (5.68MB)
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...
| Published in: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease |
|---|---|
| ISSN: | 0925-4439 |
| Published: |
Elsevier BV
2024
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa67054 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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 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. |
|---|---|
| Keywords: |
Mass spectrometry; Prostate cancer; Metabolism; Extracellular vesicles; Human primary fibroblasts |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
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. |
| Issue: |
6 |
| Start Page: |
167229 |