Low Magnetic Field Exposure Alters Prostate Cancer Cell Properties

Abstract

Simple Summary: The effects of magnetic fields on health and disease have been subject to considerable research interest for the past few decades but still remain relatively poorly understood. Therefore, the identification of molecular and cellular pathways affected is of considerable importance. This study investigated the effects of very low magnetic field (LMF) exposure in a cellular model of prostate cancer (PCa), the second most common cancer diagnosed in men. Extracellular vesicles (EVs) are lipid structures released from and taken up by cells and play crucial roles in cell communication and in processes such as cancer spread via their protein and nucleic acid cargoes. Short-term (4 h) LMF exposure significantly altered the release profiles and protein content of EVs from PCa cells to a more pro-cancerous profile. We then investigated changes in several key micro-RNAs, which are regulators of cancer behaviour and indicators of cancer aggressiveness and metastasis. LMF exposure caused significant upregulation of three key oncogenic miRNAs (miR-155, miR-21, and miR-210) and significant downregulation of two key tumour-suppressive miRNAs (miR-126 and miR-200c) in the PCa cells. These changes were also associated with a significant increase in the cancer cells’ invasion capability, which is a key indicator of cancer aggressiveness. We further verified the metastatic ability of the cancer cells caused by the LMF exposure by assessing two metastasis-related proteins, matrix metalloproteinases MMP2 and MMP9, which both were significantly increased. We compared these findings with normal prostate cells, which showed fewer changes in response to LMF exposure. Our findings suggest that LMF exposure may promote a more aggressive cancer phenotype by modulating key molecular and cellular pathways, highlighting the potential therapeutic implications of magnetic field modulation in cancer treatment. Abstract: 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.