| Autor: |
Lange S; Pathobiology and Extracellular Vesicles Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK., Inal JM; Cell Communication in Disease Pathology, School of Human Sciences, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.; Biosciences Research Group, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9EU, UK., Kraev I; Electron Microscopy Suite, Faculty of Science, Technology, Engineering and Mathematics, Open University, Milton Keynes MK7 6AA, UK., Dart DA; UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK., Uysal-Onganer P; Cancer Mechanisms and Biomarkers Research Group, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK. |
| Jazyk: |
angličtina |
| Zdroj: |
Biology [Biology (Basel)] 2024 Sep 19; Vol. 13 (9). Date of Electronic Publication: 2024 Sep 19. |
| DOI: |
10.3390/biology13090734 |
| Abstrakt: |
Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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