Abstract 37P
Background
The spread of breast cancer to the brain, known as breast-to-brain metastasis, is a critical concern that needs urgent focus and solution. The identification and management of breast cancer that has spread to the brain pose significant challenges. Our goal is to uncover a new mechanism that could contribute to the metastasis of breast cancer to the brain.
Methods
Whole exome sequencing was performed on 26 to pinpoint genes that were frequently mutated in these metastatic tumours. The role of the gene known as ARFGEF 3 in the process of metastasizing to the brain was examined using techniques such as western blot, flow cytometry, qPCR, and confocal microscopy.
Results
One of the genes identified from exome sequencing was ARFGEF3. We validated through RT–PCR, western blots, and flow cytometry that the loss of ARFGEF3 resulted in an increased expression of neurotransmitter receptor components. Utilising confocal immunofluorescence microscopy, we showed that the absence of ARFGEF3 caused a rise in the levels of certain neurotransmitter receptors on the cell membrane.
Conclusions
This study introduces a new mechanism that connects breast cancer metastasis to the brain. It suggests that the loss of the ARFGEF3 gene results in the altered expression of neurotransmitter receptors, ultimately contributing to a novel pathway for breast cancer metastasis to the brain. While the formation of pseudo synapses and the activation of NMDAR and GABA receptors have recently been discovered as potential mechanisms for breast cancer metastasis to the brain, direct evidence of how the receptors form is still lacking. The loss of ARFGEF3 has been found to upregulate the expression of most neurotransmitter receptors, indicating its role in their expression. This work deciphers novel therapeutic targets, genes, and mechanisms for breast cancer metastasis to the brain. Our future research will focus on exploring the impact of neurotransmitters on breast cancer cells lacking AFRGEF3 by co-culturing these cells with neurons using a scaffold.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Wolverhampton.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.