Abstract
Background: Brain metastasis (BM) is a common and devastating complication in triple-negative breast cancer (TNBC), often associated with poor prognosis. Extravasation, a critical step in the metastatic cascade, involves the rolling of breast cancer cells (BCCs) along the brain endothelium (BE), adhesion to the BE, and subsequent trans-endothelial migration (TEM). However, the molecular mechanisms driving the expression of adhesion molecules on brain endothelial cells (BECs), which facilitate extravasation, remain poorly understood. Recently, exosomes have emerged as key regulators of carcinogenesis. In this study, we investigated the role of exosomes released by brain metastatic TNBC cells in modulating the BE and promoting trans-endothelial extravasation.
Methods: Exosomes were isolated from two human TNBC cell lines with differing brain metastatic potentials (MDA-MB-231 and MDA-MB-231-BrM2) using an exosome isolation kit. BECs were subsequently treated with these exosomes to evaluate their impact on TEM through the BE.
Results: Our findings revealed that exosomes derived from highly metastatic BCCs (MDA-MB-231-BrM2) significantly enhanced the adhesion and transmigration capabilities of the parental low-metastatic BCCs (MDA-MB-231).
Conclusion: Exosomes play a critical role in the extravasation process through the BE by inducing adhesion molecule expression. Further studies are warranted to elucidate the precise role of exosomes in BM, particularly in the extravasation of metastatic TNBC through the BE. Understanding these mechanisms could pave the way for the development of novel preventive treatments for BM.
Biography
Dr Rania Harati is Associate Professor at the College of Pharmacy, University of Sharjah, United Arab Emirates. She earned her PhD in Experimental and Clinical Pharmacology from Paris-Sud University (Paris-Saclay University) and completed her postdoctoral training at Pierre and Marie Curie University (Sorbonne University) in Paris, France. Her research focuses on understanding the regulation of the blood-brain barrier in health and disease.